Peripheral CD8+CD28- T cell level reflects tumor immunity and could predict anti- HER2 based therapy response in metastatic breast cancer

Abstract

Purpose: Despite recent clinical improvements, HER2-positive metastatic breast cancer (MBC) is still incurable. A robust biomarker is needed in predicting the efficacy of anti-HER2 based therapy. Experimental Design: A total of 252 HER-positive MBC patients received first-line therapy were retrospectively recruited at two medical centers. Peripheral lymphocyte levels of baseline and subsequent follow-up visits were detected using flow-cytometer. The cutoff value of peripheral CD8+CD28-T cell (pTCD8+CD28-) was determined by X-tile software. The levels of TILs, immune cytokines and mutation prevalence were compared between pTCD8+CD28-high (≥18.0%) and pTCD8+CD28-low. Results: The median follow-up time was 29.6 months. pTCD8+CD28-high at baseline indicates a better PFS in patients received anti-HER2 based therapy (11.1 vs. 18.9 months, P = 0.001). During the therapeutic course, patients who maintained or regain pTCD8+CD28-high had a better PFS than those maintained pTCD8+CD28-low (15.5 vs. 11.1 vs. 7.7 months, P < 0.001). The higher IL-2 level (P = 0.034) and lower TGF-β level (P = 0.016) in the serum were connected to pTCD8+CD28-high. Highly infiltrated TILs including CD8 + CD28-T cell and higher prevalence of PD-L1 deletion (P = 0.041) were associated with pTCD8+CD28-high. The elevated pTCD8+CD28-level induced by anti-PD1 therapy was also observed in triple-negative MBC patients.Conclusions: The pTCD8+CD28-level at baseline and its dynamic change are predictive for anti-HER2 based therapy. Higher pTCD8+CD28-level is associated with an enhanced tumor immunity in HER2-positive MBC. Adding anti-PD1 therapy to HER2-targeted therapy according to pTCD8+CD28-level could be a promising alternative.