Study The Synergistic Role Of Trastuzumab Along With Docetaxel In Immune Profiling Of Her2+Breast Cancer Patients

Breast cancer is the most occurring malignancy among females worldwide. According to Globocan 2018 around 34.4 % of total cancer cases, breast cancer shows higher mortality rate of 11.3% with poor survival. Among all the subtypes of breast cancer, HER2+ cases have a lower survival rate with high recurrence in both Hispanic and Caucasian population. In tumor microenvironment (TME), immune cells play diverse roles either as antitumor or pro-tumor effectors under specific cytokine stimulation. The negative immune check point markers like programmed cell death 1 (PD1), programmed cell death ligand 1 (PDL-1) and their exhaustion markers play the crucial role in cancer prognosis by suppressing the immune system in cancer progression and metastasis. The higher expression of these immunoregulatory molecules predominantly shows the poor prognosis in breast cancer malignancies. In the current chemotherapy regime for HER2+ breast cancer cases, patient receives the monoclonal antibody, trastuzumab in combination with an anti-microtubule agent docetaxel. Few recent studies showed that trastuzumab itself downregulates the PD1, PDL-1 expression and also effects the functions of tumor infiltrating lymphocytes (TILs). But the synergetic role of these chemotherapeutics in regulating immune response and disease progression are yet to be studied. In this study, we have examined the effect of both docetaxel and trastuzumab on the negative immune checkpoint markers (PDL-1, PD1, TIM3, LAG3 etc.) along with CD4+/CD8+ TILs using IHC and flowcytometry in HER2+ breast cancer patients, received neo- adjuvant chemotherapy (NACT) treatment before and adjuvant therapy after the surgery, cells isolated from tumor tissue and peripheral blood. Pre-surgery NACT patients have a high infiltration of CD4+/CD8+ ratio in tumor as well as in peripheral blood than post-surgery adjuvant treatment. Together with the increase of CD4+/CD8+ ratio, pre-surgery NACT treated group has a comparatively lower expression of negative immune checkpoint markers and the exhaustion markers. Our finding is that the NACT received before surgery decreases the expression of negative immune checkpoint markers and the exhaustion markers together with the increase of CD4+/CD8+ ratio in HER2+ breast cancer as compared with the patients with adjuvant therapy after surgery. This study will emphasize on the combine effect of two chemotherapeutic arms in the treatment regime, before and after surgery of HER2+ breast cancer that could improve the survival rate.