Tumor Infiltrating Lymphocytes and NHERF1 Impact on Prognosis of Breast Cancer Patients

Abstract

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, and patients with apparently similar clinicopathological characteristics in clinical practice show different outcome. This study evaluated in primary BCs and in the subgroup of the triple-negative breast cancers (TNBCs) the level of tumor infiltrating lymphocytes (TILs), Na+/H+ exchanger regulatory factor 1 (NHERF1) expression, and their association respect to the clinical outcome of patients. MATERIAL AND METHODS: NHERF1 expression was assessed by immunohistochemistry in 338 BC samples; the analysis of TILs was examined using hematoxylin and eosin stained slides, according to International TILs Working Group 2014. RESULTS: Multivariate analysis identified TILs as an independent prognostic factor for DFS in the entire cohort and in the TNBC subgroup (HR, 0.32; 95% CI, 0.12–0.87; P = 0.026; and HR, 0.22; 95% CI, 0.06–0.80; P = 0.022, respectively). Univariate and survival analysis by Kaplan–Meier method revealed that patients with cytoplasmic (c) NHERF1-/TILs+ expression had better DFS than other patients (P = 0.049), and this result was also found in the TNBC subgroup (P = 0.031). Moreover, TNBC patients with cNHERF1−/TILs− expression had a worse DFS and OS than other patients (P = 0.057 and P = 0.002, respectively). CONCLUSIONS: In the complex scenario of BC and in the era of tumor immunogenicity and immunotherapy, we found an association of TIL levels and cNHERF1 expression that could be useful to identify BCs and particularly TNBC patients with different prognosis and clinical outcome.

BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis

“…Immunotherapy, such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, plays a good anti-tumor effect in the treatment of malignant tumors, such as lung cancer ( Cheng et al, 2020 ; Eguren-Santamaria et al, 2020 ) and melanoma ( Cuevas and Daud, 2018 ; Albershardt et al, 2020 ). Moreover, increasing numbers of studies showed that tumor-infiltrating lymphocytes, such as tumor-associated macrophages (TAMs) and tumor-infiltrating neutrophils (TINs), were directly related to the patients’ prognosis and efficacy of immunotherapy ( Bocchialini et al, 2020 ; He et al, 2020 ; Schirosi et al, 2020 ; Stenzel et al, 2020 ). Therefore, the study of the interaction between tumor and immunity and identification of novel targets of immunotherapy are of great clinical significance for the treatment of patients.…”

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).…”

Predictive biomarkers of inhibitors immune checkpoints therapy in malignant tumors

“…Инфильтрация опухоли лимфоцитами, как показали ретроспективные исследования, связана с повышением показателей выживаемости у пациентов с различными злокачественными новообразованиями (ЗНО), такими как колоректальный рак, меланома, рак молочной железы (РМЖ) и НМРЛ [16][17][18][19]. Набольшее количество клинических исследований, изучавших прогностическую значимость опухоль-инфильтрирующих лимфоцитов (ОИЛ), было посвящено РМЖ [20,21]. Было установлено, что выраженная инфильтрация опухоли у больных РМЖ цитотоксическими CD8 + Т-клетками коррелировала с выживаемостью пациентов [22] и ответом на химиотерапию.…”