Data from In Situ Detection of Individual Classic MHC-I Gene Products in Cancer
Year: 2025
Type: other
Abstract: Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated antigens or neoantigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicates detection by IHC. In this study, we determined recognition of 16 specific HLA-A, -B, and -C alleles by 15 antibodies commercially available for IHC use, identifying and validating pan and specific HLA-A, -B, and -C antibodies, providing a validated method that can be applied to investigate HLA-A, -B, and -C molecule–specific loss in cancer. We applied this approach to a series of breast cancers as a proof of utility, identifying differential HLA-A, -B, and -C loss, with a higher incidence of HLA-A and -B loss in hormone-driven breast cancers, HLA-B loss in HER2+ cancers, and an equal loss of all three molecules in triple-negative disease. Additionally, we found that at the protein level, HLA-A and -B loss were early events prevalent in premalignant lesions, whereas HLA-C loss was less common throughout tumor evolution. Effective response to immunotherapies such as checkpoint inhibitors and MHC-I–targeted cancer vaccines, which hinge on the carriage of specific allele groups, requires MHC-I expression on tumor cells. These findings have implications for the success of checkpoint inhibitors and vaccine strategies.
Authors: Paula I. Gonzalez-Ericsson, Susan R. Opalenik, Violeta Sanchez, Amy M. Palubinsky, Ann Hanna, Xiaopeng Sun, Andres A. Ocampo, Guadalupe Garcia, Leonel Maldonado, Zaida Morante, Tatiana Vidaurre, Guillermo Valencia, Henry L. Gomez, Melinda E. Sanders, Laura C. Kennedy, Elizabeth J. Phillips, Justin M. Balko
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4409079405