Research ExplorerPublicationsDistribution and prognostic relevance of tumor-infiltrating ...

Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases

Standard

Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. / Harter, Patrick N; Bernatz, Simon; Scholz, Alexander; Zeiner, Pia S; Zinke, Jenny; Kiyose, Makoto; Blasel, Stella; Beschorner, Rudi; Senft, Christian; Bender, Benjamin; Ronellenfitsch, Michael W; Wikman-Kocher, Harriet; Glatzel, Markus; Meinhardt, Matthias; Juratli, Tareq A; Steinbach, Joachim P; Plate, Karl H; Wischhusen, Jörg; Weide, Benjamin; Mittelbronn, Michel.

In: ONCOTARGET, Vol. 6, No. 38, 12.2015, p. 40836-40849.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Harter, PN, Bernatz, S, Scholz, A, Zeiner, PS, Zinke, J, Kiyose, M, Blasel, S, Beschorner, R, Senft, C, Bender, B, Ronellenfitsch, MW, Wikman-Kocher, H, Glatzel, M, Meinhardt, M, Juratli, TA, Steinbach, JP, Plate, KH, Wischhusen, J, Weide, B & Mittelbronn, M 2015, 'Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases', ONCOTARGET, vol. 6, no. 38, pp. 40836-40849. https://doi.org/10.18632/oncotarget.5696

APA

Harter, P. N., Bernatz, S., Scholz, A., Zeiner, P. S., Zinke, J., Kiyose, M., Blasel, S., Beschorner, R., Senft, C., Bender, B., Ronellenfitsch, M. W., Wikman-Kocher, H., Glatzel, M., Meinhardt, M., Juratli, T. A., Steinbach, J. P., Plate, K. H., Wischhusen, J., Weide, B., & Mittelbronn, M. (2015). Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. ONCOTARGET, 6(38), 40836-40849. https://doi.org/10.18632/oncotarget.5696

Vancouver

Harter PN, Bernatz S, Scholz A, Zeiner PS, Zinke J, Kiyose M et al. Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. ONCOTARGET. 2015 Dec;6(38):40836-40849. https://doi.org/10.18632/oncotarget.5696

Bibtex

@article{42e1adce22d7408d9ddfe40b5101f485,
title = "Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases",
abstract = "The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.",
author = "Harter, {Patrick N} and Simon Bernatz and Alexander Scholz and Zeiner, {Pia S} and Jenny Zinke and Makoto Kiyose and Stella Blasel and Rudi Beschorner and Christian Senft and Benjamin Bender and Ronellenfitsch, {Michael W} and Harriet Wikman-Kocher and Markus Glatzel and Matthias Meinhardt and Juratli, {Tareq A} and Steinbach, {Joachim P} and Plate, {Karl H} and J{\"o}rg Wischhusen and Benjamin Weide and Michel Mittelbronn",
year = "2015",
month = dec,
doi = "10.18632/oncotarget.5696",
language = "English",
volume = "6",
pages = "40836--40849",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "38",

}

RIS

TY - JOUR

T1 - Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases

AU - Harter, Patrick N

AU - Bernatz, Simon

AU - Scholz, Alexander

AU - Zeiner, Pia S

AU - Zinke, Jenny

AU - Kiyose, Makoto

AU - Blasel, Stella

AU - Beschorner, Rudi

AU - Senft, Christian

AU - Bender, Benjamin

AU - Ronellenfitsch, Michael W

AU - Wikman-Kocher, Harriet

AU - Glatzel, Markus

AU - Meinhardt, Matthias

AU - Juratli, Tareq A

AU - Steinbach, Joachim P

AU - Plate, Karl H

AU - Wischhusen, Jörg

AU - Weide, Benjamin

AU - Mittelbronn, Michel

PY - 2015/12

Y1 - 2015/12

N2 - The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.

AB - The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.

U2 - 10.18632/oncotarget.5696

DO - 10.18632/oncotarget.5696

M3 - SCORING: Journal article

C2 - 26517811

VL - 6

SP - 40836

EP - 40849

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 38

ER -