CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma

Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+&...
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Autor*in:	Andrea Katharina Lindner [verfasserIn] Agnieszka Martowicz [verfasserIn] Gerold Untergasser [verfasserIn] Johannes Haybaeck [verfasserIn] Eva Compérat [verfasserIn] Florian Kocher [verfasserIn] Andreas Seeber [verfasserIn] Martin Thurnher [verfasserIn] Renate Pichler [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 15(2023), 4, p 1001
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:4, p 1001

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers15041001

Katalog-ID:	DOAJ080992382

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520			\|a Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC.
650		4	\|a CXCR3 expression
650		4	\|a chemokines
650		4	\|a renal cell carcinoma
650		4	\|a recurrence
650		4	\|a immunohistochemistry
650		4	\|a adjuvant immunotherapy
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
700	0		\|a Agnieszka Martowicz \|e verfasserin \|4 aut
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700	0		\|a Martin Thurnher \|e verfasserin \|4 aut
700	0		\|a Renate Pichler \|e verfasserin \|4 aut
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allfields	10.3390/cancers15041001 doi (DE-627)DOAJ080992382 (DE-599)DOAJ7aaba224bc5142c799f9dcbaa78dd73d DE-627 ger DE-627 rakwb eng RC254-282 Andrea Katharina Lindner verfasserin aut CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC. CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Agnieszka Martowicz verfasserin aut Gerold Untergasser verfasserin aut Johannes Haybaeck verfasserin aut Eva Compérat verfasserin aut Florian Kocher verfasserin aut Andreas Seeber verfasserin aut Martin Thurnher verfasserin aut Renate Pichler verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4, p 1001 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4, p 1001 https://doi.org/10.3390/cancers15041001 kostenfrei https://doaj.org/article/7aaba224bc5142c799f9dcbaa78dd73d kostenfrei https://www.mdpi.com/2072-6694/15/4/1001 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2023 4, p 1001
spelling	10.3390/cancers15041001 doi (DE-627)DOAJ080992382 (DE-599)DOAJ7aaba224bc5142c799f9dcbaa78dd73d DE-627 ger DE-627 rakwb eng RC254-282 Andrea Katharina Lindner verfasserin aut CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC. CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Agnieszka Martowicz verfasserin aut Gerold Untergasser verfasserin aut Johannes Haybaeck verfasserin aut Eva Compérat verfasserin aut Florian Kocher verfasserin aut Andreas Seeber verfasserin aut Martin Thurnher verfasserin aut Renate Pichler verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4, p 1001 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4, p 1001 https://doi.org/10.3390/cancers15041001 kostenfrei https://doaj.org/article/7aaba224bc5142c799f9dcbaa78dd73d kostenfrei https://www.mdpi.com/2072-6694/15/4/1001 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2023 4, p 1001
allfields_unstemmed	10.3390/cancers15041001 doi (DE-627)DOAJ080992382 (DE-599)DOAJ7aaba224bc5142c799f9dcbaa78dd73d DE-627 ger DE-627 rakwb eng RC254-282 Andrea Katharina Lindner verfasserin aut CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC. CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Agnieszka Martowicz verfasserin aut Gerold Untergasser verfasserin aut Johannes Haybaeck verfasserin aut Eva Compérat verfasserin aut Florian Kocher verfasserin aut Andreas Seeber verfasserin aut Martin Thurnher verfasserin aut Renate Pichler verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4, p 1001 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4, p 1001 https://doi.org/10.3390/cancers15041001 kostenfrei https://doaj.org/article/7aaba224bc5142c799f9dcbaa78dd73d kostenfrei https://www.mdpi.com/2072-6694/15/4/1001 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2023 4, p 1001
allfieldsGer	10.3390/cancers15041001 doi (DE-627)DOAJ080992382 (DE-599)DOAJ7aaba224bc5142c799f9dcbaa78dd73d DE-627 ger DE-627 rakwb eng RC254-282 Andrea Katharina Lindner verfasserin aut CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC. CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Agnieszka Martowicz verfasserin aut Gerold Untergasser verfasserin aut Johannes Haybaeck verfasserin aut Eva Compérat verfasserin aut Florian Kocher verfasserin aut Andreas Seeber verfasserin aut Martin Thurnher verfasserin aut Renate Pichler verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4, p 1001 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4, p 1001 https://doi.org/10.3390/cancers15041001 kostenfrei https://doaj.org/article/7aaba224bc5142c799f9dcbaa78dd73d kostenfrei https://www.mdpi.com/2072-6694/15/4/1001 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2023 4, p 1001
allfieldsSound	10.3390/cancers15041001 doi (DE-627)DOAJ080992382 (DE-599)DOAJ7aaba224bc5142c799f9dcbaa78dd73d DE-627 ger DE-627 rakwb eng RC254-282 Andrea Katharina Lindner verfasserin aut CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC. CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Agnieszka Martowicz verfasserin aut Gerold Untergasser verfasserin aut Johannes Haybaeck verfasserin aut Eva Compérat verfasserin aut Florian Kocher verfasserin aut Andreas Seeber verfasserin aut Martin Thurnher verfasserin aut Renate Pichler verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4, p 1001 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4, p 1001 https://doi.org/10.3390/cancers15041001 kostenfrei https://doaj.org/article/7aaba224bc5142c799f9dcbaa78dd73d kostenfrei https://www.mdpi.com/2072-6694/15/4/1001 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2023 4, p 1001
language	English
source	In Cancers 15(2023), 4, p 1001 volume:15 year:2023 number:4, p 1001
sourceStr	In Cancers 15(2023), 4, p 1001 volume:15 year:2023 number:4, p 1001
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Andrea Katharina Lindner @@aut@@ Agnieszka Martowicz @@aut@@ Gerold Untergasser @@aut@@ Johannes Haybaeck @@aut@@ Eva Compérat @@aut@@ Florian Kocher @@aut@@ Andreas Seeber @@aut@@ Martin Thurnher @@aut@@ Renate Pichler @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ080992382
language_de	englisch
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Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. 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callnumber-first	R - Medicine
author	Andrea Katharina Lindner
spellingShingle	Andrea Katharina Lindner misc RC254-282 misc CXCR3 expression misc chemokines misc renal cell carcinoma misc recurrence misc immunohistochemistry misc adjuvant immunotherapy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma
authorStr	Andrea Katharina Lindner
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topic_title	RC254-282 CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma CXCR3 expression chemokines renal cell carcinoma recurrence immunohistochemistry adjuvant immunotherapy
topic	misc RC254-282 misc CXCR3 expression misc chemokines misc renal cell carcinoma misc recurrence misc immunohistochemistry misc adjuvant immunotherapy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc CXCR3 expression misc chemokines misc renal cell carcinoma misc recurrence misc immunohistochemistry misc adjuvant immunotherapy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc CXCR3 expression misc chemokines misc renal cell carcinoma misc recurrence misc immunohistochemistry misc adjuvant immunotherapy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma
ctrlnum	(DE-627)DOAJ080992382 (DE-599)DOAJ7aaba224bc5142c799f9dcbaa78dd73d
title_full	CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma
author_sort	Andrea Katharina Lindner
journal	Cancers
journalStr	Cancers
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author_browse	Andrea Katharina Lindner Agnieszka Martowicz Gerold Untergasser Johannes Haybaeck Eva Compérat Florian Kocher Andreas Seeber Martin Thurnher Renate Pichler
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author-letter	Andrea Katharina Lindner
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title_sort	cxcr3 expression is associated with advanced tumor stage and grade influencing survival after surgery of localised renal cell carcinoma
callnumber	RC254-282
title_auth	CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma
abstract	Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC.
abstractGer	Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC.
abstract_unstemmed	Background: Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8<sup<+</sup< T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8<sup<+</sup< T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. Methods: CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Results: Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that <i<CXCR3</i< was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (<i<p</i< = 0.0044) and grade (<i<p</i< = 0.0518), correlating significantly with a higher CD8<sup<+</sup< T cell expression (<i<p</i< < 0.001). Patients with CXCR3<sup<high</sup< RCCs had also a significant shorter RFS compared to CXCR3<sup<low</sup< (median: 78 vs. 147 months, <i<p</i< = 0.0213). In addition, also tumor stage pT3/4 (<i<p</i< < 0.0001) as well as grade G3/4 (<i<p</i< = 0.0008) negatively influenced RFS. Conclusion: CXCR3<sup<high</sup< cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC.
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title_short	CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma
url	https://doi.org/10.3390/cancers15041001 https://doaj.org/article/7aaba224bc5142c799f9dcbaa78dd73d https://www.mdpi.com/2072-6694/15/4/1001 https://doaj.org/toc/2072-6694
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CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma

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