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Immune response predicts longer OS for ovarian cancer

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November 30, 2017

Matthew Block

Women with high-grade serous ovarian cancer and high levels of cytotoxic CD8 appeared to have longer OS than those with low or no CD8, suggesting the presence of the cells may be a prognostic factor for patients, according to study results.

“This study shows the higher the level of cytotoxic CD8 tumor-infiltrating lymphocytes in a tumor, the better the survival for patients with high-grade ovarian cancer,” Matthew Block, MD, PhD, oncologist at Mayo Clinic and researcher with the Ovarian Tumor Tissue Analysis (OTTA) Consortium, said in a press release. “Developing a better understanding of factors that increase cytotoxic CD8 tumor-infiltrating lymphocytes will be the key to developing treatments to achieve better outcomes in treating patients with high-grade ovarian cancer.”

Previous research showed ovarian cancer prognosis to be associated with tumor-infiltrating lymphocytes at the time of cytoreductive surgery. However, little is known about the role of cytotoxic CD8 cells and their ability to fight against the disease.

Block and colleagues reviewed tumor samples from 7,377 women with a primary diagnosis of epithelial ovarian, peritoneal or fallopian tube cancer. Immunohistochemical analysis included 5,577 patients, 3,196 of whom had high-grade serous ovarian carcinomas.

The mean age at diagnosis was 58.4 years (median, 58.2 years).

Researchers divided and assessed patients based on their estimated number of CD8-positive tumor-infiltrating lymphocytes per high-powered field: negative (0), low (1-2), moderate (3-19) and high (> 20).

The association between CD8 and survival — determined via penalized B-splines — served as the primary objective.

Patients with high-grade serous ovarian carcinomas showed the most infiltration compared with other histotypes. CD8-positive tumor-infiltrating lymphocytes appeared significantly associated with longer OS.

Median survival was 2.8 years for patients without CD8-positive tumor-infiltrating lymphocytes compared with 3 years for patients with low levels, 3.8 years for patients with moderate levels and 5.1 years for patients with high levels (P =4.2×1016).

Researchers observed a survival benefit associated with increasing levels of CD8-positive tumor-infiltrating lymphocytes among women with endometrioid (P = .008) and mucinous (P = .04) carcinomas, but not for those with other histotypes.

Among high-grade carcinomas, CD8-positive tumor-infiltrating lymphocytes had a favorable effect regardless of stage of residual disease after cytoreduction and standard treatment.

However, the extent of CD8-positive tumor-infiltrating lymphocytes differed by mutation status (P = .02). Among 133 patients with germline BRCA1 mutation, 29% had high tumor-infiltrating lymphocytes compared with 18% of noncarriers and 15% of BRCA2 mutation carriers.

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The survival benefit associated with CD8-positive tumor-infiltrating lymphocytes also differed by mutation status. High CD8-positive tumor-infiltrating lymphocytes were linked to favorable survival among patients without mutations (P = 5.1 ×107), as well as among patients with BRCA1 mutation (P = .003). Researchers observed no association between survival and CD8 tumor-infiltrating lymphocytes among BRCA2 mutation carriers.

“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 researchers wrote. – by Melinda Stevens

 

Disclosures: Block reports no relevant disclosures. Please see the full study for all other authors’ relevant financial disclosures.

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