Tumor infiltrating lymphocytes and homologous recombination deficiency are independently associated with improved survival in ovarian carcinoma

Gynecologic Oncology
Christopher B MorseElizabeth M Swisher

Abstract

The presence of tumor infiltrating lymphocytes (TIL) and defects in homologous recombination (HR) are each important prognostic factors in ovarian carcinoma (OC). We characterized the association between HR deficiency (HRD) and the presence of TILs in a cohort of OC patients and the relative contribution to overall survival. Patients with carcinoma of the ovary, fallopian tube, or peritoneum were prospectively enrolled. Malignant neoplasm and serum samples were collected. Immunohistochemistry for CD3+ T cells and CD68+ tumor associated macrophages (TAMs) was performed on specimens collected at primary surgery. Damaging germline and somatic mutations in genes in the HR-mediated repair (HRR) pathway were identified using BROCA sequencing. HRD was defined as a damaging mutation in one of 12 genes in the HRR pathway or promoter hypermethylation in BRCA1 or RAD51C. Ninety-eight of 250 patients included in the analysis had HRD OC (39.2%). HRD OC were enriched for CD3+ TILs and CD68+ TAMs. High CD3+ TIL was present in 65.3% of HRD OC compared to 43.4% of non-HRD OC (P = 0.001). High CD68+ TAM was present in 66.3% of HRD OC compared to 50.7% of non-HRD OC (P = 0.015). Patients with HRD OC and high CD3+ TILs had the longest median overa...Continue Reading

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Citations

Mar 21, 2020·Nature Communications·Anniina FärkkiläPanagiotis A Konstantinopoulos
Jul 23, 2019·Journal of Gynecologic Oncology·Junsik ParkSunghoon Kim
Nov 4, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Tarek TahaRuth Perets
Feb 25, 2020·Bulletin du cancer·Olivia Le SauxIsabelle Ray-Coquard
Aug 24, 2021·Therapeutic Advances in Medical Oncology·Alexandra LearyJonathan Ledermann
Nov 18, 2021·Immunotherapy·Christo KoleDimitrios Schizas

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