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