PD-L1 Amino Acid Position 88 Represents a Hotspot for PD-L1 Stability With Relevance for PD-L1 Inhibition.

The two most common antibody targeting principles in oncology are the induction of direct antitumor effects and the release of antitumor T cell immunity by immune checkpoint blockade. These two principles, however, may be overlapping if the targeted checkpoint molecule is not located on the immune cell but on the tumor cell itself. Secondary resistance by epitope escape may therefore remain a challenge in both settings. We previously reported epitope escape through L88S and truncating programmed cell death ligand 1 (PD-L1) gene mutations in colorectal cancer patients on selective pressure with avelumab, a PD-L1-directed checkpoint blocker that-in addition to T cell disinhibition-allows direct tumor cell killing

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Copyright © 2022 Claaß, Schultheiß, Scholz, Paschold, Simnica, Heinemann, Stintzing and Binder.

Déclaration de conflit d'intérêts

SS received honoraria for talks and advisory board role from Amgen, Astra-Zeneca, Bayer, BMS, ESAI, LEO Pharma, Lilly, Merck KGaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, and Takeda and research funding from Merck KGaA, Pierre-Fabre, Servier, and Roche. VH received honoraria for talks and advisory board role from Merck, Amgen, Roche, Sanofi, Sirtex, Servier, Pfizer, Pierre-Fabre, AstraZeneca, BMS, MSD, Novartis, Boehringer Ingelheim, Pierre-Fabre, Celgene, Terumo, Oncosil, and Seagen and research funding from Merck, Amgen, Roche, Sanofi, Pfizer, Boehringer-Ingelheim, Sirtex, and Servier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.