Relationship between immune checkpoint proteins and neoadjuvant chemotherapy response in breast cancer

Abstract

Introduction: Following major developments in cancer immunotherapy, treatments targeting immune checkpoint proteins (ICP) gained interest in breast cancer, though studies mostly focus on patients with metastatic disease as well as patients nonresponsive to the conventional treatments. Herein, we aimed to investigate the levels of ICP in tumor stroma and tumor infiltrating lymphocytes, and tumor tissue prior to neoadjuvant chemotherapy administration to evaluate the relationship between ICP levels, clinicopathological parameters, and NAC response.

Materials and methods: This study was conducted with 51 patients where PD-1, PD-L1, CTLA-4, TIM-3, CD24 and CD44 levels were investigated in CD45⁺ cells while CD326, CD24, CD44 and PD-L1 protein expression levels were investigated in CD45^- population. In addition, CD44 and CD24 levels were evaluated in the tumor stroma. TIL levels were investigated according to the TILS Working Group. Treatment responses after NAC were evaluated according to the MD Anderson RCB score.

Results: Our results revealed positive correlation between CTLA-4 and CD44 expression in cases with high TIL levels as well as TIL levels and CTLA-4 expression in cases with partial response. Similarly, positive correlation was detected between TIM3 and PD-L1 levels in cases with good response. In addition, a negative correlation between TILs after NAC and PD-1/PD-L1 expression in lymphocytes in cases with partial complete response.

Conclusions: Our study provides preliminary data about the correlation between ICP and clinicopathological status and NAC response in breast cancer, in addition to underlining the requirement for further research to determine their potential as therapeutic targets.

Keywords: Breast cancer; CTLA-4; Immune checkpoint proteins; Neoadjuvant chemotherapy; PD-1; TIM-3.