Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab

Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868). Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Maria Grazia Narducci [verfasserIn] Anna Tosi [verfasserIn] Alessandra Frezzolini [verfasserIn] Enrico Scala [verfasserIn] Francesca Passarelli [verfasserIn] Laura Bonmassar [verfasserIn] Alessandro Monopoli [verfasserIn] Maria Pina Accetturi [verfasserIn] Maria Cantonetti [verfasserIn] Gian Carlo Antonini Cappellini [verfasserIn] Federica De Galitiis [verfasserIn] Antonio Rosato [verfasserIn] Mario Picozza [verfasserIn] Giandomenico Russo [verfasserIn] Stefania D’Atri [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 11(2020)
Übergeordnetes Werk:	volume:11 ; year:2020

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2020.579894

Katalog-ID:	DOAJ01425574X

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allfields	10.3389/fimmu.2020.579894 doi (DE-627)DOAJ01425574X (DE-599)DOAJ1c8fc2a673d54b849a6b8725c0c206c0 DE-627 ger DE-627 rakwb eng RC581-607 Maria Grazia Narducci verfasserin aut Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868). cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B Immunologic diseases. Allergy Anna Tosi verfasserin aut Alessandra Frezzolini verfasserin aut Enrico Scala verfasserin aut Francesca Passarelli verfasserin aut Laura Bonmassar verfasserin aut Alessandro Monopoli verfasserin aut Maria Pina Accetturi verfasserin aut Maria Cantonetti verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Federica De Galitiis verfasserin aut Antonio Rosato verfasserin aut Antonio Rosato verfasserin aut Mario Picozza verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 11(2020) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:11 year:2020 https://doi.org/10.3389/fimmu.2020.579894 kostenfrei https://doaj.org/article/1c8fc2a673d54b849a6b8725c0c206c0 kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2020.579894/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
spelling	10.3389/fimmu.2020.579894 doi (DE-627)DOAJ01425574X (DE-599)DOAJ1c8fc2a673d54b849a6b8725c0c206c0 DE-627 ger DE-627 rakwb eng RC581-607 Maria Grazia Narducci verfasserin aut Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868). cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B Immunologic diseases. Allergy Anna Tosi verfasserin aut Alessandra Frezzolini verfasserin aut Enrico Scala verfasserin aut Francesca Passarelli verfasserin aut Laura Bonmassar verfasserin aut Alessandro Monopoli verfasserin aut Maria Pina Accetturi verfasserin aut Maria Cantonetti verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Federica De Galitiis verfasserin aut Antonio Rosato verfasserin aut Antonio Rosato verfasserin aut Mario Picozza verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 11(2020) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:11 year:2020 https://doi.org/10.3389/fimmu.2020.579894 kostenfrei https://doaj.org/article/1c8fc2a673d54b849a6b8725c0c206c0 kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2020.579894/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfields_unstemmed	10.3389/fimmu.2020.579894 doi (DE-627)DOAJ01425574X (DE-599)DOAJ1c8fc2a673d54b849a6b8725c0c206c0 DE-627 ger DE-627 rakwb eng RC581-607 Maria Grazia Narducci verfasserin aut Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868). cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B Immunologic diseases. Allergy Anna Tosi verfasserin aut Alessandra Frezzolini verfasserin aut Enrico Scala verfasserin aut Francesca Passarelli verfasserin aut Laura Bonmassar verfasserin aut Alessandro Monopoli verfasserin aut Maria Pina Accetturi verfasserin aut Maria Cantonetti verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Federica De Galitiis verfasserin aut Antonio Rosato verfasserin aut Antonio Rosato verfasserin aut Mario Picozza verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 11(2020) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:11 year:2020 https://doi.org/10.3389/fimmu.2020.579894 kostenfrei https://doaj.org/article/1c8fc2a673d54b849a6b8725c0c206c0 kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2020.579894/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsGer	10.3389/fimmu.2020.579894 doi (DE-627)DOAJ01425574X (DE-599)DOAJ1c8fc2a673d54b849a6b8725c0c206c0 DE-627 ger DE-627 rakwb eng RC581-607 Maria Grazia Narducci verfasserin aut Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868). cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B Immunologic diseases. Allergy Anna Tosi verfasserin aut Alessandra Frezzolini verfasserin aut Enrico Scala verfasserin aut Francesca Passarelli verfasserin aut Laura Bonmassar verfasserin aut Alessandro Monopoli verfasserin aut Maria Pina Accetturi verfasserin aut Maria Cantonetti verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Federica De Galitiis verfasserin aut Antonio Rosato verfasserin aut Antonio Rosato verfasserin aut Mario Picozza verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 11(2020) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:11 year:2020 https://doi.org/10.3389/fimmu.2020.579894 kostenfrei https://doaj.org/article/1c8fc2a673d54b849a6b8725c0c206c0 kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2020.579894/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsSound	10.3389/fimmu.2020.579894 doi (DE-627)DOAJ01425574X (DE-599)DOAJ1c8fc2a673d54b849a6b8725c0c206c0 DE-627 ger DE-627 rakwb eng RC581-607 Maria Grazia Narducci verfasserin aut Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868). cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B Immunologic diseases. Allergy Anna Tosi verfasserin aut Alessandra Frezzolini verfasserin aut Enrico Scala verfasserin aut Francesca Passarelli verfasserin aut Laura Bonmassar verfasserin aut Alessandro Monopoli verfasserin aut Maria Pina Accetturi verfasserin aut Maria Cantonetti verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Federica De Galitiis verfasserin aut Antonio Rosato verfasserin aut Antonio Rosato verfasserin aut Mario Picozza verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 11(2020) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:11 year:2020 https://doi.org/10.3389/fimmu.2020.579894 kostenfrei https://doaj.org/article/1c8fc2a673d54b849a6b8725c0c206c0 kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2020.579894/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
language	English
source	In Frontiers in Immunology 11(2020) volume:11 year:2020
sourceStr	In Frontiers in Immunology 11(2020) volume:11 year:2020
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Maria Grazia Narducci @@aut@@ Anna Tosi @@aut@@ Alessandra Frezzolini @@aut@@ Enrico Scala @@aut@@ Francesca Passarelli @@aut@@ Laura Bonmassar @@aut@@ Alessandro Monopoli @@aut@@ Maria Pina Accetturi @@aut@@ Maria Cantonetti @@aut@@ Gian Carlo Antonini Cappellini @@aut@@ Federica De Galitiis @@aut@@ Antonio Rosato @@aut@@ Mario Picozza @@aut@@ Giandomenico Russo @@aut@@ Stefania D’Atri @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ01425574X
language_de	englisch
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callnumber-first	R - Medicine
author	Maria Grazia Narducci
spellingShingle	Maria Grazia Narducci misc RC581-607 misc cutaneous T-cell lymphoma misc PD-1 blockade therapy misc immune sub-populations misc Ki67 proliferation index misc granzyme B misc Immunologic diseases. Allergy Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab
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topic_title	RC581-607 Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab cutaneous T-cell lymphoma PD-1 blockade therapy immune sub-populations Ki67 proliferation index granzyme B
topic	misc RC581-607 misc cutaneous T-cell lymphoma misc PD-1 blockade therapy misc immune sub-populations misc Ki67 proliferation index misc granzyme B misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc cutaneous T-cell lymphoma misc PD-1 blockade therapy misc immune sub-populations misc Ki67 proliferation index misc granzyme B misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc cutaneous T-cell lymphoma misc PD-1 blockade therapy misc immune sub-populations misc Ki67 proliferation index misc granzyme B misc Immunologic diseases. Allergy
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title	Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab
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title_full	Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab
author_sort	Maria Grazia Narducci
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author_browse	Maria Grazia Narducci Anna Tosi Alessandra Frezzolini Enrico Scala Francesca Passarelli Laura Bonmassar Alessandro Monopoli Maria Pina Accetturi Maria Cantonetti Gian Carlo Antonini Cappellini Federica De Galitiis Antonio Rosato Mario Picozza Giandomenico Russo Stefania D’Atri
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title_sort	reduction of t lymphoma cells and immunological invigoration in a patient concurrently affected by melanoma and sezary syndrome treated with nivolumab
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title_auth	Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab
abstract	Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868).
abstractGer	Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868).
abstract_unstemmed	Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients’ response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations. In blood, we observed a progressive reduction of SS cell number and a raise in the percentage of normal CD4+ and CD8+ T cells and NK cells over total leukocytes. Eight weeks from the start of nivolumab, these immune cell subsets showed an increase of Ki67 proliferation index that positively correlated with their PD-1 expression. Conversely, SS cells displayed a strong reduction of Ki67 positivity despite their high PD-1 expression. On skin biopsies we observed a marked reduction of SS cells which were no more detectable at the end of therapy. We also found an increase in the percentage of normal CD4+ T cells with a concomitant decrease of that of CD8+ and CD4+ CD8+ T cells, two cell subsets that, however, acquired a cytotoxic phenotype. In summary, our study demonstrated that nivolumab marked reduced SS tumor burden and invigorated immune responses in our patient. Our data also suggest, for the first time, that Ki67 expression in circulating neoplastic and immune cell subsets, as well as an enrichment in T cells with a cytotoxic phenotype in lesional skin could be valuable markers to assess early on treatment SS patients’ response to PD-1 blockade, a therapeutic strategy under clinical investigation in CTCL (ClinicalTrials.gov NCT03385226, NCT04118868).
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title_short	Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab
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