Expression Of Immune Control Point Inhibitor (Pd-1, Tim-3, Lag-3 And Tigit) On Tumor Infiltrating Lymphocytes In In Situ And Invasive Ductal Breast Carcinomas And Its Relationship With Prognostic Factors


Thesis Type: Expertise In Medicine

Institution Of The Thesis: Gazi University, Tıp Fakültesi, Turkey

Approval Date: 2020

Thesis Language: Turkish

Student: Dr. Elif ACAR

Supervisor: AYŞE DURSUN

Abstract:

Breast cancer is the most common cancer in women and its frequency is increasing worldwide. Recently, immunotherapy has been determined as an important choice, especially in tumors which markedly inflammatory response. In studies about this subject, it has been found that immuno-control point receptors are highly expressed in tumor-infiltrating lymphocytes. In this subject tumor infiltrating lymphocytes (TIL) and the expression of immune control point receptors on TIL has gained importance. In our study, stromal TIL rates and tertiary lymphoid structures were determined in 312 invasive, 68 in situ breast cancer. With the immunohistochemical study, PD-1, LAG-3 and TIM-3 expressions on intratumoral and stromal TIL were investigated. In invasive breast carcinomas, stromal TIL was found to be associated with lymph node metastasis (p=0,040), HR and HER2 expression (p=0,001) and basal-like phenotype (p<0,001). The presence of tertiary lymphoid structuring was found to be associated with neoadjuvant therapy (p=0,025), recurrence (p=0,043), death (p=0,009), and expression of HR and HER2 (p=0,019). PD-1, LAG-3 and TIM-3 expressions were found to be associated with diagnosis, molecular classification, stromal TIL rates and tertiary lymphoid structuring. In multivariate analysis, high stromal TIL and PD-1 expression in intratumoral TIL were found to be independent prognostic 195 factors in terms of overall survival and disease-free survival. While LAG-3 and TIM-3 expressions were not statistically significant in terms of survival, cases with high expression of these receptors tend to have longer survival. In in situ breast tumors, stromal TIL was found to be associated with HER2 positivity and high nuclear grade. Evaluation of TIL and immune control point receptor expressions in breast cancer is increasingly important in terms of planning the therapeutic approaches based on immunotherapy.