PortalPublikationenHigh density of cytotoxic T-lymphocytes is linked to tumoral...

High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer

Standard

High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer. / Möller, Katharina; Blessin, Niclas C; Höflmayer, Doris; Büscheck, Franziska; Luebke, Andreas M; Kluth, Martina; Hube-Magg, Claudia; Zalewski, Katarzyna; Hinsch, Andrea; Neipp, Michael; Mofid, Hamid; Lárusson, Hannes; Daniels, Thies; Isbert, Christoph; Coerper, Stephan; Ditterich, Daniel; Rupprecht, Holger; Goetz, Albert; Bernreuther, Christian; Sauter, Guido; Uhlig, Ria; Wilczak, Waldemar; Simon, Ronald; Steurer, Stefan; Minner, Sarah; Burandt, Eike; Krech, Till; Perez, Daniel; Izbicki, Jakob R; Clauditz, Till S; Marx, Andreas H.

in: ACTA ONCOL, Jahrgang 60, Nr. 9, 09.2021, S. 1210-1217.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Möller, K, Blessin, NC, Höflmayer, D, Büscheck, F, Luebke, AM, Kluth, M, Hube-Magg, C, Zalewski, K, Hinsch, A, Neipp, M, Mofid, H, Lárusson, H, Daniels, T, Isbert, C, Coerper, S, Ditterich, D, Rupprecht, H, Goetz, A, Bernreuther, C, Sauter, G, Uhlig, R, Wilczak, W, Simon, R, Steurer, S, Minner, S, Burandt, E, Krech, T, Perez, D, Izbicki, JR, Clauditz, TS & Marx, AH 2021, 'High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer', ACTA ONCOL, Jg. 60, Nr. 9, S. 1210-1217. https://doi.org/10.1080/0284186X.2021.1933585

APA

Möller, K., Blessin, N. C., Höflmayer, D., Büscheck, F., Luebke, A. M., Kluth, M., Hube-Magg, C., Zalewski, K., Hinsch, A., Neipp, M., Mofid, H., Lárusson, H., Daniels, T., Isbert, C., Coerper, S., Ditterich, D., Rupprecht, H., Goetz, A., Bernreuther, C., ... Marx, A. H. (2021). High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer. ACTA ONCOL, 60(9), 1210-1217. https://doi.org/10.1080/0284186X.2021.1933585

Vancouver

Möller K, Blessin NC, Höflmayer D, Büscheck F, Luebke AM, Kluth M et al. High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer. ACTA ONCOL. 2021 Sep;60(9):1210-1217. https://doi.org/10.1080/0284186X.2021.1933585

Bibtex

@article{f3fdcd364c4a401aba99efdf93a3c510,
title = "High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer",
abstract = "BACKGROUND: Immune checkpoint-inhibitors targeting the PD-1/PD-L1 system are FDA approved in microsatellite instable (MSI) or mismatch repair deficient (dMMR) colorectal cancer (CRC). PD-L1 expression is tightly linked to features connected to immune checkpoint inhibitor response, but studies on large subsets of cancers analyzing the correlation between different status of MSI/dMMR, tumor infiltrating lymphocytes and PD-L1 expression are still lacking.METHODS: More than 1800 CRC were analyzed for PD-L1 by immunohistochemistry in a tissue microarray format. Data were compared to MMR, the number of intratumoral CD8+ cytotoxic T-cells, and adverse clinico-pathological parameters. Different cutoff levels for defining PD-L1 positivity in tumor cells (1%, 5%, 10%, and 50%) yielded comparable results.RESULTS: At a cutoff level of 5%, PD-L1 positivity was seen in 5.1% of tumors. PD-L1 was more often positive in dMMR (18.6%) than in MMR proficient (pMMR) cancers (4.1%; p < 0.0001). The number of intratumoral CD8+ lymphocytes was strikingly higher in PD-L1 positive (939.5 ± 118.2) than in PD-L1 negative cancers (310.5 ± 24.8). A higher number of intratumoral CD8+ lymphocytes was found in dMMR CRC (PD-L1 positive: 1999.7 ± 322.0; PD-L1 negative: 398.6 ± 128.0; p < 0.0001) compared to pMMR CRC (PD-L1 positive: 793.2 ± 124.8; PD-L1 negative: 297.2 ± 24.2; p < 0.0001). In dMMR and pMMR CRC, PD-L1 expression in tumor cells was unrelated to tumor stage, lymph node status or lymphatic/venous invasion. PD-L1 positivity in tumor associated immune cells was seen in 47.5% of cases and was significantly linked to high numbers of tumor infiltrating CD8+, low tumor stage, and absence of lymph node metastasis and lymphatic/venous invasion (p < 0.0001 each).CONCLUSION: The data support the previously suggested fact that PD-L1 expression in tumor cells is driven by extensive cytotoxic T-cell infiltration in highly immunogenic dMMR and pMMR CRC. Frequent and intense PD-L1 expression in tumor cells of dMMR CRC may contribute to the high response rates of dMMR CRC to immune checkpoint-inhibitors.",
author = "Katharina M{\"o}ller and Blessin, {Niclas C} and Doris H{\"o}flmayer and Franziska B{\"u}scheck and Luebke, {Andreas M} and Martina Kluth and Claudia Hube-Magg and Katarzyna Zalewski and Andrea Hinsch and Michael Neipp and Hamid Mofid and Hannes L{\'a}russon and Thies Daniels and Christoph Isbert and Stephan Coerper and Daniel Ditterich and Holger Rupprecht and Albert Goetz and Christian Bernreuther and Guido Sauter and Ria Uhlig and Waldemar Wilczak and Ronald Simon and Stefan Steurer and Sarah Minner and Eike Burandt and Till Krech and Daniel Perez and Izbicki, {Jakob R} and Clauditz, {Till S} and Marx, {Andreas H}",
year = "2021",
month = sep,
doi = "10.1080/0284186X.2021.1933585",
language = "English",
volume = "60",
pages = "1210--1217",
journal = "ACTA ONCOL",
issn = "0284-186X",
publisher = "informa healthcare",
number = "9",

}

RIS

TY - JOUR

T1 - High density of cytotoxic T-lymphocytes is linked to tumoral PD-L1 expression regardless of the mismatch repair status in colorectal cancer

AU - Möller, Katharina

AU - Blessin, Niclas C

AU - Höflmayer, Doris

AU - Büscheck, Franziska

AU - Luebke, Andreas M

AU - Kluth, Martina

AU - Hube-Magg, Claudia

AU - Zalewski, Katarzyna

AU - Hinsch, Andrea

AU - Neipp, Michael

AU - Mofid, Hamid

AU - Lárusson, Hannes

AU - Daniels, Thies

AU - Isbert, Christoph

AU - Coerper, Stephan

AU - Ditterich, Daniel

AU - Rupprecht, Holger

AU - Goetz, Albert

AU - Bernreuther, Christian

AU - Sauter, Guido

AU - Uhlig, Ria

AU - Wilczak, Waldemar

AU - Simon, Ronald

AU - Steurer, Stefan

AU - Minner, Sarah

AU - Burandt, Eike

AU - Krech, Till

AU - Perez, Daniel

AU - Izbicki, Jakob R

AU - Clauditz, Till S

AU - Marx, Andreas H

PY - 2021/9

Y1 - 2021/9

N2 - BACKGROUND: Immune checkpoint-inhibitors targeting the PD-1/PD-L1 system are FDA approved in microsatellite instable (MSI) or mismatch repair deficient (dMMR) colorectal cancer (CRC). PD-L1 expression is tightly linked to features connected to immune checkpoint inhibitor response, but studies on large subsets of cancers analyzing the correlation between different status of MSI/dMMR, tumor infiltrating lymphocytes and PD-L1 expression are still lacking.METHODS: More than 1800 CRC were analyzed for PD-L1 by immunohistochemistry in a tissue microarray format. Data were compared to MMR, the number of intratumoral CD8+ cytotoxic T-cells, and adverse clinico-pathological parameters. Different cutoff levels for defining PD-L1 positivity in tumor cells (1%, 5%, 10%, and 50%) yielded comparable results.RESULTS: At a cutoff level of 5%, PD-L1 positivity was seen in 5.1% of tumors. PD-L1 was more often positive in dMMR (18.6%) than in MMR proficient (pMMR) cancers (4.1%; p < 0.0001). The number of intratumoral CD8+ lymphocytes was strikingly higher in PD-L1 positive (939.5 ± 118.2) than in PD-L1 negative cancers (310.5 ± 24.8). A higher number of intratumoral CD8+ lymphocytes was found in dMMR CRC (PD-L1 positive: 1999.7 ± 322.0; PD-L1 negative: 398.6 ± 128.0; p < 0.0001) compared to pMMR CRC (PD-L1 positive: 793.2 ± 124.8; PD-L1 negative: 297.2 ± 24.2; p < 0.0001). In dMMR and pMMR CRC, PD-L1 expression in tumor cells was unrelated to tumor stage, lymph node status or lymphatic/venous invasion. PD-L1 positivity in tumor associated immune cells was seen in 47.5% of cases and was significantly linked to high numbers of tumor infiltrating CD8+, low tumor stage, and absence of lymph node metastasis and lymphatic/venous invasion (p < 0.0001 each).CONCLUSION: The data support the previously suggested fact that PD-L1 expression in tumor cells is driven by extensive cytotoxic T-cell infiltration in highly immunogenic dMMR and pMMR CRC. Frequent and intense PD-L1 expression in tumor cells of dMMR CRC may contribute to the high response rates of dMMR CRC to immune checkpoint-inhibitors.

AB - BACKGROUND: Immune checkpoint-inhibitors targeting the PD-1/PD-L1 system are FDA approved in microsatellite instable (MSI) or mismatch repair deficient (dMMR) colorectal cancer (CRC). PD-L1 expression is tightly linked to features connected to immune checkpoint inhibitor response, but studies on large subsets of cancers analyzing the correlation between different status of MSI/dMMR, tumor infiltrating lymphocytes and PD-L1 expression are still lacking.METHODS: More than 1800 CRC were analyzed for PD-L1 by immunohistochemistry in a tissue microarray format. Data were compared to MMR, the number of intratumoral CD8+ cytotoxic T-cells, and adverse clinico-pathological parameters. Different cutoff levels for defining PD-L1 positivity in tumor cells (1%, 5%, 10%, and 50%) yielded comparable results.RESULTS: At a cutoff level of 5%, PD-L1 positivity was seen in 5.1% of tumors. PD-L1 was more often positive in dMMR (18.6%) than in MMR proficient (pMMR) cancers (4.1%; p < 0.0001). The number of intratumoral CD8+ lymphocytes was strikingly higher in PD-L1 positive (939.5 ± 118.2) than in PD-L1 negative cancers (310.5 ± 24.8). A higher number of intratumoral CD8+ lymphocytes was found in dMMR CRC (PD-L1 positive: 1999.7 ± 322.0; PD-L1 negative: 398.6 ± 128.0; p < 0.0001) compared to pMMR CRC (PD-L1 positive: 793.2 ± 124.8; PD-L1 negative: 297.2 ± 24.2; p < 0.0001). In dMMR and pMMR CRC, PD-L1 expression in tumor cells was unrelated to tumor stage, lymph node status or lymphatic/venous invasion. PD-L1 positivity in tumor associated immune cells was seen in 47.5% of cases and was significantly linked to high numbers of tumor infiltrating CD8+, low tumor stage, and absence of lymph node metastasis and lymphatic/venous invasion (p < 0.0001 each).CONCLUSION: The data support the previously suggested fact that PD-L1 expression in tumor cells is driven by extensive cytotoxic T-cell infiltration in highly immunogenic dMMR and pMMR CRC. Frequent and intense PD-L1 expression in tumor cells of dMMR CRC may contribute to the high response rates of dMMR CRC to immune checkpoint-inhibitors.

U2 - 10.1080/0284186X.2021.1933585

DO - 10.1080/0284186X.2021.1933585

M3 - SCORING: Journal article

C2 - 34092167

VL - 60

SP - 1210

EP - 1217

JO - ACTA ONCOL

JF - ACTA ONCOL

SN - 0284-186X

IS - 9

ER -