Abstract PD9-02: MHC class I and PD-L1 expression in triple-negative breast cancer subtypes: impact on T-cell infiltration and clinical outcome

Abstract

Abstract Background: Triple-negative breast cancer (TNBC) is a heterogeneous group of cancer with dismal prognosis. In an effort to discover therapeutic targets, TNBC has been further stratified into molecular subtypes. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have been increasingly utilized for the treatment of TNBC. Difficulty remains, however, in appropriate patient selection for treatment, as many PD-L1-positive cancers fail to show durable responses to PD-1/PD-L1 inhibition. Major histocompatibility complex (MHC) class I molecules play a crucial role in the presentation of tumor antigenic peptides to cytotoxic T cells. Loss of MHC class I expression in tumor cells represents a possible mechanism of immunotherapeutic resistance in PD-L1-positive cancers. However, little is known about the clinical impact and value of MHC class I expression in TNBC subtypes. Thus, this study examined MHC class I expression in TNBC subtypes with attention to PD-L1 expression and T cell infiltration. Materials and methods: MHC class I and PD-L1 expression were assessed by immunohistochemistry in 256 TNBC samples using tissue microarray. Immunohistochemistry for the TNBC molecular subtype-surrogate markers [cytokeratin 5/6 (CK5/6), CK14, epidermal growth factor receptor (EGFR), and androgen receptor (AR)], CD3, and CD8 was also performed. TNBC subtypes were classified into three subtypes: basal-like (BL), luminal AR (LAR), and unclassifiable type (UN). Results: All immunohistochemical markers were interpretable in 240 cases. TNBCs were classified into BL (65.8%), LAR (11.3%), and UN (22.9%) subtypes. Loss of MHC class I expression was found in 62 of 240 (25.8%) cases and was observed in 23.4% of BL, 40.7% of LAR, and 25.9% of UN subtype. PD-L1 expression in tumor-associated immune cells (≥1%) was seen in 69.2% (166/240). Among 166 PD-L1-positive TNBC cases, loss of MHC class I expression was seen in 16.4% of BL, 31.3% of LAR, and 20.0% of UN subtype. Loss of MHC class I expression was associated with low stromal TILs density and low CD3+ and CD8+ T-cell infiltration in BL subtype. CD3+ and CD8+ T-cell infiltration in TNBC subtype had a positive correlation with PD-L1 expression. In PD-L1 positive BL subtype, MHC class I lost expression showed a lower infiltration with CD3+ and CD8+ T-cells than MHC class I intact expression. In BL subtype, PD-L1 expression was associated with better disease-free survival and loss of MHC class I expression was associated with poor overall survival. However, MHC class I and PD-L1 expressions were not independent prognostic factors for disease-free or overall survival. Conclusions: Loss of MHC class I expression was found in TNBC, including PD-L1 positive cases. In PD-L1 positive BL subtype, loss of MHC class I expression was associated with low CD3 and CD8+ T-cell infiltration. Our results suggest that the evaluation of PD-L1 and MHC class I expression together is very important for the selection of potential responders to anti-PD-1/PD-L1 therapy for the TNBCs, especially the BL subtype. Citation Format: ji shin lee, nah ihm kim, min ho park. MHC class I and PD-L1 expression in triple-negative breast cancer subtypes: impact on T-cell infiltration and clinical outcome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD9-02.