Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort

Abstract

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

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“…However, there was no discernible disparity in TILs scores when comparing young and elderly TNBC patients in another cohort of 897 TNBC patients (Vaid et al, 2020). These findings emphasize the further validation of TIL distribution as a predictive tool in young premenopausal and old postmenopausal women with aggressive disease.…”

“…Exogenous treatment is more effective when a higher percentage of the influx of lymphocytes, particularly those from the stroma, co-operate with it. In a meta-analysis study comprising 3770 individuals with elevated TILs scores, 50% of TNBC patients were predicted to respond completely to neoadjuvant chemotherapy (Vaid et al, 2020). Evidence from TNBC patients…”

“…Exogenous treatment is more effective when a higher percentage of the influx of lymphocytes, particularly those from the stroma, co‐operate with it. In a meta‐analysis study comprising 3770 individuals with elevated TILs scores, 50% of TNBC patients were predicted to respond completely to neoadjuvant chemotherapy (Vaid et al, 2020). Evidence from TNBC patients shows that an increased number of TILs is associated with more favorable outcomes of high overall and event‐free survival demonstrating that in the subset of breast carcinoma, the immune system executes a significantly vital role.…”

“…Evidence from TNBC patients shows that an increased number of TILs is associated with more favorable outcomes of high overall and event‐free survival demonstrating that in the subset of breast carcinoma, the immune system executes a significantly vital role. A higher TILs score is significantly associated with high‐grade and large tumors (Vaid et al, 2020). A systematic analysis revealed that TNBC among breast cancer subtypes comprises elevated levels of FoxP3+ Tregs cells of about 70%; ranging between 65% and 76%, and an exorbitant incidence of TILs (20%; range, 4%–37%) (Z. Li et al, 2018).…”

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“… 8 , 10 Cytokines help to recruit immune cells to local inflammatory sites, 12 , 13 , 14 resulting in the enhancement of tumor recognition by immune cells. 15 , 16 Cytokine molecules like IL‐1α, IL‐1β, IL6, IL‐10 inhibit and eliminate cancer 17 , 18 , 19 by infiltration of immune cells in local tumor masses, 20 , 21 enhancing tumor immunoediting properties, 22 , 23 , 24 , 25 patronage tumor invasion and metastasis. 26 , 27 , 28 , 29 , 30 Several reports show that cytokines take part in integrating breast cancer commencement and progression.…”