The relationship between tumor immunity and the cGAS–STING pathway in breast cancer: An immunohistochemical study

Abstract

Breast cancer (BC) is classified into four major histological subtypes, namely luminal A, luminal B, HER2, and basal-like, and its treatment is based on these subtypes. The use of immune checkpoint inhibitors against BC depends on the expression of PD-1/PD-L1. Another tumor immune system—the cGAS–STING pathway—is a potential target for cancer immunotherapy. However, the status of the cGAS–STING pathway in BC has not been fully established. Therefore, we investigated the expression status of the cGAS–STING pathway and immune-related proteins in BC. We classified 111 BCs into six groups—29 hormone receptor-positive carcinomas, 12 HER2+ carcinomas (HER2), 8 luminal-HER2 carcinomas, 26 triple-negative breast carcinomas (TNBCs), 21 lobular carcinomas (LC), and 15 carcinomas with apocrine differentiation (CAD)—and investigated the relationship between BC and tumor immunity via the cGAS—STING pathway using histopathological and immunohistochemical methods. Expression of cGAS was high in CADs (100%) and low in TNBCs (35%); STING-positive lymphocytes were high in TNBC (85%, P = 0.0054). Expression of pSTAT3 was significantly high in patients with TNBC (≥10%, 88%). The proportion of PD-L1-positive tumor cells was higher in TNBCs (54%) than in other BCs (30%). SRGN expression was significantly higher in the TNBC group than in the other BC groups (58%). Tumor immune responses may differ among tumor subtypes. The cGAS–STING pathway may be functional in TNBC and CAD but not in LC. Therefore, targeting the cGAS–STING pathway might be useful in BC, particularly TNBC and CAD.

Keywords

• Triple-negative breast cancer
• cGAS
• pSTAT3
• STING