High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients
At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dys...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Zhang, Jingxin [verfasserIn] Ren, Ziyuan [verfasserIn] Hu, Yun [verfasserIn] Shang, Shijie [verfasserIn] Wang, Ruiyang [verfasserIn] Ma, Jiachun [verfasserIn] Zhang, Zengfu [verfasserIn] Wu, Meng [verfasserIn] Wang, Fei [verfasserIn] Yu, Jinming [verfasserIn] Chen, Dawei [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: International immunopharmacology - Amsterdam [u.a.] : Elsevier Science, 2001, 127 |
|---|---|
| Übergeordnetes Werk: |
volume:127 |
| DOI / URN: |
10.1016/j.intimp.2023.111363 |
|---|
| Katalog-ID: |
ELV066529913 |
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| 520 | |a At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. | ||
| 650 | 4 | |a Hematopoietic progenitor kinase 1 | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Non-small cell lung cancer | |
| 650 | 4 | |a Prognosis | |
| 650 | 4 | |a CD8+ T cells | |
| 700 | 1 | |a Ren, Ziyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Shijie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ruiyang |e verfasserin |0 (orcid)0000-0002-6800-5698 |4 aut | |
| 700 | 1 | |a Ma, Jiachun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zengfu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jinming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Dawei |e verfasserin |0 (orcid)0000-0002-6762-7997 |4 aut | |
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10.1016/j.intimp.2023.111363 doi (DE-627)ELV066529913 (ELSEVIER)S1567-5769(23)01690-9 DE-627 ger DE-627 rda eng 610 VZ PHARM DE-84 fid 44.38 bkl Zhang, Jingxin verfasserin aut High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. Hematopoietic progenitor kinase 1 Immunotherapy Non-small cell lung cancer Prognosis CD8+ T cells Ren, Ziyuan verfasserin aut Hu, Yun verfasserin aut Shang, Shijie verfasserin aut Wang, Ruiyang verfasserin (orcid)0000-0002-6800-5698 aut Ma, Jiachun verfasserin aut Zhang, Zengfu verfasserin aut Wu, Meng verfasserin aut Wang, Fei verfasserin aut Yu, Jinming verfasserin aut Chen, Dawei verfasserin (orcid)0000-0002-6762-7997 aut Enthalten in International immunopharmacology Amsterdam [u.a.] : Elsevier Science, 2001 127 Online-Ressource (DE-627)330614630 (DE-600)2049924-3 (DE-576)259272272 1878-1705 nnns volume:127 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ AR 127 |
| spelling |
10.1016/j.intimp.2023.111363 doi (DE-627)ELV066529913 (ELSEVIER)S1567-5769(23)01690-9 DE-627 ger DE-627 rda eng 610 VZ PHARM DE-84 fid 44.38 bkl Zhang, Jingxin verfasserin aut High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. Hematopoietic progenitor kinase 1 Immunotherapy Non-small cell lung cancer Prognosis CD8+ T cells Ren, Ziyuan verfasserin aut Hu, Yun verfasserin aut Shang, Shijie verfasserin aut Wang, Ruiyang verfasserin (orcid)0000-0002-6800-5698 aut Ma, Jiachun verfasserin aut Zhang, Zengfu verfasserin aut Wu, Meng verfasserin aut Wang, Fei verfasserin aut Yu, Jinming verfasserin aut Chen, Dawei verfasserin (orcid)0000-0002-6762-7997 aut Enthalten in International immunopharmacology Amsterdam [u.a.] : Elsevier Science, 2001 127 Online-Ressource (DE-627)330614630 (DE-600)2049924-3 (DE-576)259272272 1878-1705 nnns volume:127 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ AR 127 |
| allfields_unstemmed |
10.1016/j.intimp.2023.111363 doi (DE-627)ELV066529913 (ELSEVIER)S1567-5769(23)01690-9 DE-627 ger DE-627 rda eng 610 VZ PHARM DE-84 fid 44.38 bkl Zhang, Jingxin verfasserin aut High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. Hematopoietic progenitor kinase 1 Immunotherapy Non-small cell lung cancer Prognosis CD8+ T cells Ren, Ziyuan verfasserin aut Hu, Yun verfasserin aut Shang, Shijie verfasserin aut Wang, Ruiyang verfasserin (orcid)0000-0002-6800-5698 aut Ma, Jiachun verfasserin aut Zhang, Zengfu verfasserin aut Wu, Meng verfasserin aut Wang, Fei verfasserin aut Yu, Jinming verfasserin aut Chen, Dawei verfasserin (orcid)0000-0002-6762-7997 aut Enthalten in International immunopharmacology Amsterdam [u.a.] : Elsevier Science, 2001 127 Online-Ressource (DE-627)330614630 (DE-600)2049924-3 (DE-576)259272272 1878-1705 nnns volume:127 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ AR 127 |
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10.1016/j.intimp.2023.111363 doi (DE-627)ELV066529913 (ELSEVIER)S1567-5769(23)01690-9 DE-627 ger DE-627 rda eng 610 VZ PHARM DE-84 fid 44.38 bkl Zhang, Jingxin verfasserin aut High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. Hematopoietic progenitor kinase 1 Immunotherapy Non-small cell lung cancer Prognosis CD8+ T cells Ren, Ziyuan verfasserin aut Hu, Yun verfasserin aut Shang, Shijie verfasserin aut Wang, Ruiyang verfasserin (orcid)0000-0002-6800-5698 aut Ma, Jiachun verfasserin aut Zhang, Zengfu verfasserin aut Wu, Meng verfasserin aut Wang, Fei verfasserin aut Yu, Jinming verfasserin aut Chen, Dawei verfasserin (orcid)0000-0002-6762-7997 aut Enthalten in International immunopharmacology Amsterdam [u.a.] : Elsevier Science, 2001 127 Online-Ressource (DE-627)330614630 (DE-600)2049924-3 (DE-576)259272272 1878-1705 nnns volume:127 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ AR 127 |
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10.1016/j.intimp.2023.111363 doi (DE-627)ELV066529913 (ELSEVIER)S1567-5769(23)01690-9 DE-627 ger DE-627 rda eng 610 VZ PHARM DE-84 fid 44.38 bkl Zhang, Jingxin verfasserin aut High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. Hematopoietic progenitor kinase 1 Immunotherapy Non-small cell lung cancer Prognosis CD8+ T cells Ren, Ziyuan verfasserin aut Hu, Yun verfasserin aut Shang, Shijie verfasserin aut Wang, Ruiyang verfasserin (orcid)0000-0002-6800-5698 aut Ma, Jiachun verfasserin aut Zhang, Zengfu verfasserin aut Wu, Meng verfasserin aut Wang, Fei verfasserin aut Yu, Jinming verfasserin aut Chen, Dawei verfasserin (orcid)0000-0002-6762-7997 aut Enthalten in International immunopharmacology Amsterdam [u.a.] : Elsevier Science, 2001 127 Online-Ressource (DE-627)330614630 (DE-600)2049924-3 (DE-576)259272272 1878-1705 nnns volume:127 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 Pharmakologie VZ AR 127 |
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Zhang, Jingxin @@aut@@ Ren, Ziyuan @@aut@@ Hu, Yun @@aut@@ Shang, Shijie @@aut@@ Wang, Ruiyang @@aut@@ Ma, Jiachun @@aut@@ Zhang, Zengfu @@aut@@ Wu, Meng @@aut@@ Wang, Fei @@aut@@ Yu, Jinming @@aut@@ Chen, Dawei @@aut@@ |
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Zhang, Jingxin |
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Zhang, Jingxin ddc 610 fid PHARM bkl 44.38 misc Hematopoietic progenitor kinase 1 misc Immunotherapy misc Non-small cell lung cancer misc Prognosis misc CD8+ T cells High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients |
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610 VZ PHARM DE-84 fid 44.38 bkl High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients Hematopoietic progenitor kinase 1 Immunotherapy Non-small cell lung cancer Prognosis CD8+ T cells |
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High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients |
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High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients |
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high hpk1 + pd-1 + tim-3 + cd8 + t cells infiltration predicts poor prognosis to immunotherapy in nsclc patients |
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High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients |
| abstract |
At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. |
| abstractGer |
At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. |
| abstract_unstemmed |
At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy. |
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High HPK1 + PD-1 + TIM-3 + CD8 + T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients |
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Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. 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