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MHC-II May Be Predictor of Immunotherapy Response in HR+, Triple-Negative Breast Cancers


The study, according to the researchers, is the first to demonstrate the potential use of major histocompatibility complex class II (MHC-II) expression as a predictor of immunotherapy response in these patients.

A biomarker used to predict response to immunotherapy for patients with melanoma could also prove useful in patients with breast cancer, suggests new research, which found that major histocompatibility complex class II (MHC-II) protein may be a predictor of response for 2 types of breast cancer, including a particularly difficult-to-treat form of the disease.

The authors of the tissue-based study analyzed samples from hundreds of patients with breast cancer, finding that MHC-II was expressed in 15% of primary triple-negative breast cancer (TNBC) samples and 10% of high-risk, estrogen receptor-positive (HR+) samples.

"These findings are particularly exciting for us, because if validated, they could provide a better way to personalize therapy for breast cancer patients,” commented Justin Balko, PhD, associate professor of medicine and pathology, microbiology and immunology at Vanderbilt University Medical Center, and the study's senior author, in a statement. “So far, the typical biomarkers like PD-L1 expression and the numbers of immune cells in the tumor have not done a good job of identifying patients who need immunotherapy.”

The researchers believe the study is the first to demonstrate the potential use of MHC-II as a predictor of immunotherapy response in these patients. If further studies prove MHC-II to be a reliable marker for response to immunotherapy, testing for the molecule could help determine which patients do not need to receive immunotherapy, preventing possible treatment complications and added costs, explained the researchers.

Throughout their assessment, the researchers found that the presence of MHC-II on the tumor cells was predictive of response to durvalumab in combination with neoadjuvant chemotherapy (NAC) and pembrolizumab in combination with NAC. Notably, it was not predictive of response to NAC alone.

“The pre-defined cut point of 5% used in melanoma proved to be useful for breast cancer in the neoadjuvant setting,” wrote the researchers. “In the KEYNOTE-522 study, the addition of pembrolizumab to NAC yielded an improvement in [pathologic complete response (pCR)] rate from 54.9% to 68.9%, or a 14% change, while in the IMPassion031 trial, the addition of atezolizumab improved pCR rates from 41% to 58%, or a 17% change. Thus, in a biomarker assessment of immunotherapy benefit in a single-arm trial, approximately 20% to 30% of responding patients should be identified by the biomarker (sensitivity), while most biomarker-negative patients should be predicted to have RD (specificity). The 5% cut point approximated these sensitivity and specificity values.”

With MHC-II having shown predictive benefit in melanoma, Hodgkin lymphoma, and now potentially breast cancer, the researchers of the study suggest the molecule could prove to be a pan-cancer biomarker for predicting response to immunotherapies.


Gonzalez-Ericsson P, Wulfkuhle J, Gallagher R, et al. Tumor-specific major histocompatibility-II expression predicts benefit to anti-PD-1/L1 therapy in HER2-negative primary breast cancer. Clin Cancer Res. Published online July 27, 2021. doi:10.1158/1078-0432.CCR-21-0607

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