Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer
Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate...
Ausführliche Beschreibung
Autor*in: |
He, Xing [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Anmerkung: |
© The Author(s) 2023. corrected publication 2024 |
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Übergeordnetes Werk: |
Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 21(2023), 1 vom: 12. Okt. |
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Übergeordnetes Werk: |
volume:21 ; year:2023 ; number:1 ; day:12 ; month:10 |
Links: |
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DOI / URN: |
10.1186/s12967-023-04589-3 |
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Katalog-ID: |
SPR053387171 |
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520 | |a Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. | ||
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700 | 1 | |a Zhou, Zhenyu |4 aut | |
700 | 1 | |a Li, Wenbin |4 aut | |
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10.1186/s12967-023-04589-3 doi (DE-627)SPR053387171 (SPR)s12967-023-04589-3-e DE-627 ger DE-627 rakwb eng He, Xing verfasserin aut Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023. corrected publication 2024 Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. Tumor microenvironment (dpeaa)DE-He213 Tumor-infiltrating lymphocytes (dpeaa)DE-He213 Immune checkpoint inhibitors (dpeaa)DE-He213 Tumor biomarkers (dpeaa)DE-He213 Peng, Yaorong aut He, Gui aut Ye, Huilin aut Liu, Liqiang aut Zhou, Qixian aut Shi, Juanyi aut Fu, Sha aut Wang, Jie aut Zhou, Zhenyu aut Li, Wenbin aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 12. Okt. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:12 month:10 https://dx.doi.org/10.1186/s12967-023-04589-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 21 2023 1 12 10 |
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10.1186/s12967-023-04589-3 doi (DE-627)SPR053387171 (SPR)s12967-023-04589-3-e DE-627 ger DE-627 rakwb eng He, Xing verfasserin aut Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023. corrected publication 2024 Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. Tumor microenvironment (dpeaa)DE-He213 Tumor-infiltrating lymphocytes (dpeaa)DE-He213 Immune checkpoint inhibitors (dpeaa)DE-He213 Tumor biomarkers (dpeaa)DE-He213 Peng, Yaorong aut He, Gui aut Ye, Huilin aut Liu, Liqiang aut Zhou, Qixian aut Shi, Juanyi aut Fu, Sha aut Wang, Jie aut Zhou, Zhenyu aut Li, Wenbin aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 12. Okt. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:12 month:10 https://dx.doi.org/10.1186/s12967-023-04589-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 21 2023 1 12 10 |
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10.1186/s12967-023-04589-3 doi (DE-627)SPR053387171 (SPR)s12967-023-04589-3-e DE-627 ger DE-627 rakwb eng He, Xing verfasserin aut Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023. corrected publication 2024 Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. Tumor microenvironment (dpeaa)DE-He213 Tumor-infiltrating lymphocytes (dpeaa)DE-He213 Immune checkpoint inhibitors (dpeaa)DE-He213 Tumor biomarkers (dpeaa)DE-He213 Peng, Yaorong aut He, Gui aut Ye, Huilin aut Liu, Liqiang aut Zhou, Qixian aut Shi, Juanyi aut Fu, Sha aut Wang, Jie aut Zhou, Zhenyu aut Li, Wenbin aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 12. Okt. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:12 month:10 https://dx.doi.org/10.1186/s12967-023-04589-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 21 2023 1 12 10 |
allfieldsGer |
10.1186/s12967-023-04589-3 doi (DE-627)SPR053387171 (SPR)s12967-023-04589-3-e DE-627 ger DE-627 rakwb eng He, Xing verfasserin aut Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023. corrected publication 2024 Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. Tumor microenvironment (dpeaa)DE-He213 Tumor-infiltrating lymphocytes (dpeaa)DE-He213 Immune checkpoint inhibitors (dpeaa)DE-He213 Tumor biomarkers (dpeaa)DE-He213 Peng, Yaorong aut He, Gui aut Ye, Huilin aut Liu, Liqiang aut Zhou, Qixian aut Shi, Juanyi aut Fu, Sha aut Wang, Jie aut Zhou, Zhenyu aut Li, Wenbin aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 12. Okt. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:12 month:10 https://dx.doi.org/10.1186/s12967-023-04589-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 21 2023 1 12 10 |
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10.1186/s12967-023-04589-3 doi (DE-627)SPR053387171 (SPR)s12967-023-04589-3-e DE-627 ger DE-627 rakwb eng He, Xing verfasserin aut Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023. corrected publication 2024 Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. Tumor microenvironment (dpeaa)DE-He213 Tumor-infiltrating lymphocytes (dpeaa)DE-He213 Immune checkpoint inhibitors (dpeaa)DE-He213 Tumor biomarkers (dpeaa)DE-He213 Peng, Yaorong aut He, Gui aut Ye, Huilin aut Liu, Liqiang aut Zhou, Qixian aut Shi, Juanyi aut Fu, Sha aut Wang, Jie aut Zhou, Zhenyu aut Li, Wenbin aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 12. Okt. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:12 month:10 https://dx.doi.org/10.1186/s12967-023-04589-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 21 2023 1 12 10 |
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He, Xing @@aut@@ Peng, Yaorong @@aut@@ He, Gui @@aut@@ Ye, Huilin @@aut@@ Liu, Liqiang @@aut@@ Zhou, Qixian @@aut@@ Shi, Juanyi @@aut@@ Fu, Sha @@aut@@ Wang, Jie @@aut@@ Zhou, Zhenyu @@aut@@ Li, Wenbin @@aut@@ |
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He, Xing |
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He, Xing misc Tumor microenvironment misc Tumor-infiltrating lymphocytes misc Immune checkpoint inhibitors misc Tumor biomarkers Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer |
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Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer Tumor microenvironment (dpeaa)DE-He213 Tumor-infiltrating lymphocytes (dpeaa)DE-He213 Immune checkpoint inhibitors (dpeaa)DE-He213 Tumor biomarkers (dpeaa)DE-He213 |
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increased co-expression of pd1 and tim3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer |
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Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer |
abstract |
Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. © The Author(s) 2023. corrected publication 2024 |
abstractGer |
Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. © The Author(s) 2023. corrected publication 2024 |
abstract_unstemmed |
Background The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC. © The Author(s) 2023. corrected publication 2024 |
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Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer |
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Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. Methods We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. Results We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. Conclusions Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumor microenvironment</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumor-infiltrating lymphocytes</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immune checkpoint inhibitors</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumor biomarkers</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Peng, Yaorong</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">He, Gui</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ye, Huilin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liu, Liqiang</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Qixian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Shi, Juanyi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fu, Sha</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Jie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Zhenyu</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, Wenbin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of translational medicine</subfield><subfield code="d">London : BioMed Central, 2003</subfield><subfield code="g">21(2023), 1 vom: 12. 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