Immune checkpoint blockade therapy (ICBT) is a first-line treatment option for patients with pleural mesothelioma with the approval of ipilimumab and nivolumab. It has been challenging to identify predictive biomarkers of benefit with ICBT in mesothelioma given its low tumor mutation burden. Since ICBTs enable adaptive anti-tumor immune responses, we investigated T-cell receptor (TCR) associations with survival outcomes from participants of two ICBT clinical trials.

Immunotherapy has emerged as a frontline treatment option for malignant pleural mesothelioma (MPM) with the recent approval of the combination of the PD-1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab. Whereas tumors with high mutation burdens are typically responsive to immunotherapy, MPM reportedly has a very low mutation burden, which is inconsistent with other tumors related to carcinogen exposures. We previously demonstrated that chromosomal rearrangements are common and have neoantigenic potential in MPM.