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

Abstract

BackgroundThe 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.MethodsHER2-positive MBC patients with no prior therapy in the metastatic setting were retrospectively recruited at two medical centres. Peripheral CD8 + CD28− T cells (pTCD8+CD28-) were detected at baseline and following therapeutic intervals. Progression-free survival (PFS) was compared according to pTCD8+CD28− levels. The molecular features of pTCD8+CD28− and its correlation with tumour immunity were also investigated.ResultsA total of 252 patients were enrolled, and the median follow-up time was 29.6 months. pTCD8+CD28− high at baseline has prolonged PFS compared to pTCD8+CD28− low (P = 0.001). Patients who maintained pTCD8+CD28− high had a longer PFS than those who kept pTCD8+CD28− low (P < 0.001). The enhanced pTCD8+CD28− level also indicates a longer PFS compared to pTCD8+CD28− low (P = 0.025). Here, pTCD8+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 pTCD8+CD28− high.ConclusionsHigh pTCD8+CD28− level is associated with a favourable tumour immunity and a better PFS of HER2-targeting therapy in MBC patients.