The breast cancer immune microenvironment is modified by neoadjuvant chemotherapy

Abstract

Neoadjuvant chemotherapy (NAT) in breast cancer (BC) has been used to reduce tumor burden prior to surgery. However, the impact on prognosis depends on the establishment of Pathological Complete Response (pCR), which is influenced by tumor-infiltrating lymphocyte levels and the activation of the antitumor immune response. Nonetheless, NAT can affect immune infiltration and the quality of the response. Here, we showed that NAT induces dynamic changes in the tumor microenvironment (TME). After NAT, an increase of regulatory T cells and a decrease of CD8+ T cells was found in tumor, correlated with the presence of metastatic cells in lymph nodes. In addition, an increase of polymorphonuclear myeloid-derived suppressor like cells was found in luminal patients post-NAT. pCR patients showed a balance between the immune populations, while non-pCR patients presented an inverse relationship in the frequency of CD68+ versus CD3+, CD8+, and CD20+ cells. Moreover, activated T cells were found in peripheral blood, as well as an increase in T cell clonality with a lower diversity post-NAT. Overall, these results shown that NAT induces an activation of immune response, however, a balance in the TME seems to be related to a better antigenic presentation and therefore a better response to treatment.

Immune Lymphocyte Infiltrate and its Prognostic Value in Triple-Negative Breast Cancer

“…We cannot rule out that there may be misclassified cases among studies and that this may explain, in part, why some studies did not find statistically significant differences in some of the outcomes evaluated. It is also important to consider if TILs were evaluated in resected specimens from patients who previously received neoadjuvant chemotherapy since it is well known that chemotherapy can modify the panorama of the immune infiltrate, and this could impact the results of TIL characterization (94)(95)(96).…”

Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

“…In breast cancer, a 12-chemokine signature capable of predicting the presence of TLSs is shown to be prognostic for improved survival [ 15 ]. Concurrently, the presence of histologically-detected TLSs is prognostic for OS in TNBC [ 16 ] and related to improved DFS and OS across multiple breast cancer subtypes [ 17 , 62 ]. TLSs are found in different stages of maturity [ 63 ] and are typically transient.…”

“…Accordingly, high or increased levels of total TIL counts post-NACT compared to baseline levels have been associated with residual disease or poor outcomes in patients with inflammatory TNBC [ 100 ]. However, further investigation is required to fully delineate the clinical significance of post-NACT TIL counts due to conflicting and variable results [ 17 , 101 , 102 , 103 ]. Across all breast cancer subtypes, intratumoural CD8+ T cells are increased after NACT; meanwhile, the total CD3+ T cell compartment and the proportions of CD3+ CD4+ T cells and CD20+ B cells are reduced [ 104 ].…”

Immune response in colorectal carcinoma: a review of its significance as a predictive and prognostic biomarker

“…Little is known about the effect of therapy on the tumour immune microenvironment in colorectal carcinoma 93–95 . Similar to results in breast cancer, 96,97 neoadjuvant therapy in colorectal cancer can result in activation of the immune response leading to better antigenic presentation and better response to treatment in some, but not all, patients.…”