Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility

Abstract

The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tumor-infiltrating lymphocytes are promising further predictive utility in view of novel immune-related therapeutic strategies which are coming into the clinical setting launching a solid rationale for the future next-generation treatment options. In this scenario, tumor-infiltrating lymphocytes might represent an important resource for the selection of the most appropriate therapeutic strategy, as well as further evaluations of the molecular mechanisms underlying tumor-infiltrating lymphocytes and the immunoediting process would eventually provide new insights to augment therapeutic success. Considering these perspectives, we review the potential utility of tumor-infiltrating lymphocytes in the definition of breast cancer prognosis and in the prediction of treatment outcomes, along with the new promising molecular-based therapeutic discoveries.

Ex vivo expanded natural killer cells from breast cancer patients and healthy donors are highly cytotoxic against breast cancer cell lines and patient-derived tumours

“…NK cell infusion shortly after chemotherapy would act to repopulate the patient with their own, highly activated NK cells, and subsequently restore NK cell function. While the primary goal of chemotherapy is to decrease tumour size, it is also known that chemotherapy affects immune cell populations and tumour cell surface marker expression [48]. The increased expression of cancer antigens and immunogenic molecules induced by chemotherapy on tumour cells could be favourable for the function of the infused NK cells.…”

“…The increased expression of cancer antigens and immunogenic molecules induced by chemotherapy on tumour cells could be favourable for the function of the infused NK cells. In addition, increased apoptosis in immunoregulatory cells, such as regulatory T cells and MDSCs, has also been observed following chemotherapy, which would better support NK cell activation [48]. …”

Neutrophil to Lymphocyte Ratio as Prognostic and Predictive Factor in Breast Cancer Patients: A Systematic Review

“…In recent years, the role of tumor infiltrating lymphocytes (TILs), especially in BC, has also been studied [12]. TILs are a selected population of T cells that show a high specific immunological reactivity against tumor cells.…”

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

“…TIL levels are higher in highly proliferating tumors, including human epidermal growth factor receptor 2 (HER2)-positive and TNBC (3). TILs have a strong prognostic and predictive significance, and high TIL levels are positively correlated with pathological complete response rate and patient survival rate (4)(5)(6)(7).…”