Th2 infiltration is a better predictor of survival than tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC)

Abstract

AbstractPurposeTriple-negative breast cancers (TNBC) account for 15% of all breast cancers but carry the worst prognosis. Because of their heterogenicity, these tumors are not all prone to targeted therapies. However, due to their high immune infiltration, targeting their immune microenvironment is of tremendous interest and is becoming the standard of care for high-risk early-stage TNBC. Nevertheless, the characterization of this immune infiltrate is often limited to general tumor-infiltrating lymphocytes (TILs) counting, without characterization of lymphocytes subtypes. Thus, we aimed at precisely characterizing these sub-populations and evaluating their prognostic significance.MethodsWe selected 91 TNBC tumors for which we had both the TILs count on hematoxylin and eosin (H&E) slides determined by an expert pathologist and the immune microenvironment cell subtypes characterization using flow cytometry (FC). We then compared the prognostic value of immune microenvironment subpopulations vs total TILs count.ResultsTNBCs contained a mean of 22.8±25.9% TILs in the tumor surface area, including mainly CD4+ helper T lymphocytes (14.1%), mostly Th2 (11.7%), CD8+ cytotoxic T lymphocytes (11.1%), and myeloid cells (8.4%) including antigen presenting cells (APC). The TILs count was correlated with the abundance of these cellular subpopulations (p≤0.004). TILs percentage was predictive of overall survival (OS) in univariate analysis (p=0.044), high APC infiltration was predictive of relapse-free survival (RFS) in univariate analysis (p≤0.030), and Th2 infiltration was predictive of both RFS and OS in univariate (p=0.009, 0.008 respectively) and multivariate analyses (p=0.002, 0.010 respectively).ConclusionThe characterization of TILs composition is essential to better understand the potential antitumoral functions of these cells, and to strongly improve the associated prognostic and predictive values. We here demonstrate that Th2 subpopulation is associated with a better overall survival in TNBC and could be of use to predict response to the newly used immunotherapies.