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    Tumor-Infiltrating Lymphocytes (TIL), Tertiary Lymphoid Structures (TLS), and Expression of PD-1, TIM-3, LAG-3 on TIL in Invasive and In Situ Ductal Breast Carcinomas and Their Relationship with Prognostic Factors
    (Cig Media Group, Lp, 2022) Acar, Elif; Esendagli, Guldal; Yazici, Ozan; Dursun, Ayse
    We wanted to evaluate the expression of immune checkpoint receptors in pathology samples to support research on whether the immune response against breast cancer can be used for treatment. For this purpose, we studied 312 invasive and 68 in situ breast cancers. We found that PD-1 and stromal TIL were associated with survival. Determination of PD-1 expression on stromal TIL can provide information about whether the patient can benefit from immunotherapy. Introduction: Immunotherapy has been determined as an important choice in breast carcinomas, especially in tumors with markedly inflammatory response. About this promising subject, tumor-infiltrating lymphocytes (TIL) and the expression of immune control point receptors on TIL have gained importance. Materials and Methods: In this study, stromal TIL and tertiary lymphoid structures (TLS) were determined in tumor tissues of 312 invasive and 68 in situ breast cancer patients. Expression rates of PD-1, LAG-3, and TIM-3 on intratumoral and stromal TIL were immunohistochemically evaluated. Results: In invasive breast carcinomas, stromal TIL was found to be significantly associated with lymph node metastasis, HR and HER2 expression, and basal-like phenotype, as the presence of TLS with neoadjuvant therapy, recurrence, death, and expression of HR and HER2. PD-1, LAG-3, and TIM-3 expressions were found to be associated with HR and HER2 status, stromal TIL rates, and TLS. In multivariate analysis, high stromal TIL and PD-1 expression in intratumoral TIL were found to be independent prognostic factors in terms of overall survival and disease-free survival. Conclusion: Evaluation of TIL and immune control point receptor expressions in breast cancer is particularly important in terms of planning the therapeutic approaches based on immunotherapy protocols.