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. 2024 Sep 13;30(18):4077-4081.
doi: 10.1158/1078-0432.CCR-24-1286.

Associations of Immune Checkpoint Predictive Biomarkers (MHC-I and MHC-II) with Clinical and Molecular Features in a Diverse Breast Cancer Cohort

Xiaopeng Sun  1 , Laura C Kennedy  1   2 , Paula I Gonzalez-Ericsson  1   2 , Violeta Sanchez  1 , Melinda Sanders  1   2   3 , Charles M Perou  4 , Melissa A Troester  4 , Justin M Balko  1   2   3 , Sonya A Reid  1   2
Affiliations

Associations of Immune Checkpoint Predictive Biomarkers (MHC-I and MHC-II) with Clinical and Molecular Features in a Diverse Breast Cancer Cohort

Xiaopeng Sun et al. Clin Cancer Res. .

Abstract

Purpose: Immunotherapy (IO) in triple-negative breast cancer (TNBC) has improved survival outcomes, with promising improvements in pCR rates among early high-risk hormone receptor (HR)+/HER2- breast cancers. However, biomarkers are needed to select patients likely to benefit from IO. MHC-I and tumor-specific MHC-II (tsMHC-II) expression are candidate biomarkers for PD-(L)1 checkpoint inhibition but existing data from clinical trials included limited racial/ethnic diversity.

Experimental design: We performed multiplexed immunofluorescence assays in the Carolina Breast Cancer Study (CBCS; n = 1,628, 48% Black, 52% non-Black). Intrinsic subtype and P53 mutant-like status were identified using RNA-based multigene assays. We ranked participants based on tumoral MHC-I intensity (top 33% categorized as "MHC-Ihigh") and MHC-II+ (≥5% of tumor cells as tsMHC-II+). MHC-I/II were evaluated in association with clinicopathological features by race.

Results: Black participants had higher frequency of TNBC (25% vs. 12.5%, P ≤ 0.001) and basal-like (30% vs. 14%, P ≤ 0.001) tumors overall, and higher frequency of basal-like (11% vs. 5.5%, P = 0.002) and TP53 mutant tumors (26% vs. 17%, P = 0.002) among HR+/HER2-. The frequency of tsMHC-II+ was higher in HR+/HER2- Black participants (7.9% vs. 4.9%, P = 0.04). Black participants also had higher frequency of MHC-Ihigh (38.7% vs. 28.2%, P < 0.001), which was significant among HR+/HER2- (28.2% vs. 22.1%, P = 0.02).

Conclusions: In this diverse study population, MHC-I and MHC-II tumor cell expression were more highly expressed in HR+/HER2- tumors from Black women, underscoring the importance of diverse and equitable enrollment in future IO trials.

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Conflict of interest statement

Conflict of Interests

Justin Balko receives research support from Genentech/Roche and Incyte Corporation, has received advisory board payments from AstraZeneca, Eli Lilly, and Mallinckrodt and is an inventor on patents regarding immunotherapy targets and biomarkers in cancer. Charles M. Perou is an equity stockholder and consultant of BioClassifier LLC; Charles M. Perou is also listed as an inventor on patent applications for the Breast PAM50 Subtyping assay. Laura C. Kennedy has research support from Puma Biotechnologies and Hoffmann-Roche and consulting fees from Daiichi-Sankyo. The other authors disclosed no conflicts of interest.

Figures

Figure 1:
Figure 1:. MHC-I and MHC-II expression is associated with Race.
The relative frequency difference of tumors having (A) high MHC-I expression (ranked top 33% based on percentage of MHC-I positive tumor) and (B) ≥ 5% tumor cells expressing MHC-II are compared between Black and Non-Black patients. Relative frequency difference calculated using Non-Black as control condition, with positive RFD representing frequency higher in Black patients. Bootstrap method used to generate standard errors.
See this image and copyright information in PMC

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