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

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Acar E., ESENDAĞLI G., YAZICI O., DURSUN A.

Clinical Breast Cancer, vol.22, no.8, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.1016/j.clbc.2022.08.005
  • Journal Name: Clinical Breast Cancer
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE
  • Keywords: Immune checkpoint molecules, Tumor immunology, Immunotherapy, Breast cancer treatment, Breast cancer prognosis
  • Gazi University Affiliated: Yes

Abstract

© 2022 Elsevier Inc.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.