Deciphering the Immunopeptidomic Landscape in Melanoma

As cancer-specific antigens are uncurbed by immune tolerance, and their expression is restricted to the diseased tissue, they constitute attractive therapeutic targets. Indeed, the identification of neoantigens has enabled the generation of personalized therapeutic cancer vaccines. Yet, despite the great achievements in the field, personalized immunotherapies are still limited to specific cancer types due to the lack of targetable antigen identification and their design suffers from complexities involved in selecting the cancer-antigens to target. Our lab aims to decipher the composition of the cancer immunopeptidome presented by MHC-I and MHC-II molecules and specifically, reveal the nature of mutated and aberrant peptides presented by malignant cells. This will enable a broader application of cancer vaccine-based immunotherapies, and is highly relevant to our understanding of immune surveillance.

Further reading: 

Peri, A. et al. The landscape of T cell antigens for cancer immunotherapy. Nat Cancer 4, 937-954 (2023)

Kalaora, S., Nagler, A., Wargo, J. A. & Samuels, Y. Mechanisms of immune activation and regulation: lessons from melanoma. Nat Rev Cancer 22, 195-207 (2022)

Nagler, A. et al. Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics. Cell Rep 35 (2021)

Peri, A. et al. Combined presentation and immunogenicity analysis reveals a recurrent RAS.Q61K neoantigen in melanoma. J Clin Invest 131 (2021)

Kalaora, S. et al. Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma. Cancer Discov 8, 1366-1375 (2018)

Robbins, P. F. et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 19, 747-+ (2013)