Persistence of peripheral CD8 + CD28− T cells indicates a favourable outcome and tumour immunity in first-line HER2-positive metastatic breast cancer

Background The contradictory role of CD8 + CD28− T cells in tumour immunity has been reported, while their biological and clinical significance in HER2-positive metastatic breast cancer (MBC) is still unknown. Methods HER2-positive MBC patients with no prior therapy in the metastatic setting were retrospectively recruited at two medical centres. Peripheral CD8 + CD28− T cells (pT CD8+CD28- ) were detected at baseline and following therapeutic intervals. Progression-free survival (PFS) was compared according to pT CD8+CD28− levels. The molecular features of pT CD8+CD28− and its correlation with tumour immunity were also investigated. Results A total of 252 patients were enrolled, and the median follow-up time was 29.6 months. pT CD8+CD28− high at baseline has prolonged PFS compared to pT CD8+CD28− low ( P = 0.001). Patients who maintained pT CD8+CD28− high had a longer PFS than those who kept pT CD8+CD28− low ( P < 0.001). The enhanced pT CD8+CD28− level also indicates a longer PFS compared to pT CD8+CD28− low ( P = 0.025). Here, pT CD8+CD28- was demonstrated as an antigen-experienced effector T cell. Higher IL-2 level ( P = 0.034) and lower TGF-β level ( P = 0.016) in the serum and highly infiltrated CD8 + CD28− T cells ( P = 0.037) were also connected to pT CD8+CD28− high. Conclusions High pT CD8+CD28− level is associated with a favourable tumour immunity and a better PFS of HER2-targeting therapy in MBC patients.