TILs AND SURVIVAL IN OVARIAN CANCER

As reported in JAMA Oncology by Goode et al in the Ovarian Tumor Tissue Analysis Consortium, higher levels of cytotoxic CD8-positive tumor-infiltrating lymphocytes were associated with significantly improved overall survival among women with high-grade serous ovarian carcinomas.

Study Details

The study involved 5,577 women with primary diagnosis of epithelial ovarian, peritoneal, or fallopian tube cancer, including 3,196 with high-grade serous ovarian high-grade serous ovarian carcinoma. Patients were followed prospectively for > 24,650 person-years. CD8-positive tumor-infiltrating lymphocytes were identified within epithelial components of tumor islets, with patients grouped according to the number of CD8-positive tumor-infiltrating lymphocytes per high-powered field as negative (none), low (1–2), moderate (3–19), or high (≥ 20).

Associations With Survival

Among the five major invasive ovarian cancer histotypes, CD8-positive tumor-infiltrating lymphocytes were found in 83% of high-grade serous ovarian carcinomas, 73% of low-grade serous ovarian cancers, 72% of endometrioid cancers, 52% of clear cell cancers, and 51% of mucinous cancers. Among patients with high-grade serous ovarian carcinoma, the median overall survival was 2.8 years for those with no CD8-positive tumor-infiltrating lymphocytes and 3.0, 3.8, and 5.1 years for those with low, moderate, and high levels of CD8-positive tumor-infiltrating lymphocytes (P value for trend = 4.2 × 10-16), respectively. Among high-grade serous ovarian carcinomas, the presence of CD8-positive tumor-infiltrating lymphocytes was favorable irrespective of the extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 mutation but was not associated with benefit in BRCA2-mutation carriers.

Increasing levels of CD8-positive tumor-infiltrating lymphocytes were also associated with longer survival among women with endometrioid ovarian cancer (P value for trend = .008) and those with mucinous ovarian cancer (P value for trend= .04).

The investigators concluded: “This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ [tumor-infiltrating lymphocytes] and [high-grade serous ovarian carcinoma] survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.”

The study was funded by the Canadian Institutes for Health Research, the Brazilian National Council for Scientific and Technological Development, Calgary Laboratory Services, German Federal Ministry of Education and Research, U.S. National Cancer Institute, and others.

Ellen L. Goode, PhD, MPH, of the Mayo Clinic, Rochester, is the corresponding author of the JAMA Oncologyarticle.