Tumor MHC Expression Guides First-Line Immunotherapy Selection in Melanoma.

Abstract

Immunotherapy targeting T-cell inhibitory receptors, namely programmed cell death-1 (PD-1) and/or cytotoxic T-lymphocyte associated protein-4 (CTLA-4), leads to durable responses in a proportion of patients with advanced metastatic melanoma. Combination immunotherapy results in higher rates of response compared to anti-PD-1 monotherapy, at the expense of higher toxicity. Currently, there are no robust molecular biomarkers for the selection of first-line immunotherapy. We used flow cytometry to profile pretreatment tumor biopsies from 36 melanoma patients treated with anti-PD-1 or combination (anti-PD-1 plus anti-CTLA-4) immunotherapy. A novel quantitative score was developed to determine the tumor cell expression of antigen-presenting MHC class I (MHC-I) molecules, and to correlate expression data with treatment response. Melanoma MHC-I expression was intact in all tumors derived from patients who demonstrated durable response to anti-PD-1 monotherapy. In contrast, melanoma MHC-I expression was low in 67% of tumors derived from patients with durable response to combination immunotherapy. Compared to MHC-I high tumors, MHC-I low tumors displayed reduced T-cell infiltration and a myeloid cell-enriched microenvironment. Our data emphasize the importance of robust MHC-I expression for anti-PD-1 monotherapy response and provide a rationale for the selection of combination immunotherapy as the first-line treatment in MHC-I low melanoma.

• Authors: Elena Shklovskaya, Jenny H Lee, Su Yin Lim, Ashleigh Stewart, Bernadette Pedersen, Peter Ferguson, Robyn Pm Saw, John F Thompson, Brindha Shivalingam, Matteo S Carlino, Richard A Scolyer, Alexander M Menzies, Georgina V Long, Richard F Kefford, Helen Rizos
• Journal: Cancers (Cancers (Basel)) Vol. 12 Issue 11 (Nov 14 2020) ISSN: 2072-6694 [Print] Switzerland
• PMID: 33202676 (Publication Type: Journal Article)