CD8+ TILs AS PROGNOSTIC FACTOR IN OVARIAN CANCER

In women with high-grade serous ovarian carcinomas, increasing levels of CD8+ tumor-infiltrating lymphocytes (TILs) show a robust, dose-dependent survival benefit, according to a large observational study.

In their October 12 online article in JAMA Oncology, Dr. Matthew S. Block of the Mayo Clinic, Rochester, Minnesota, and colleagues identify epithelial ovarian cancer (OC) as the most lethal gynecologic cancer even though patients may achieve initial remission. The presence of CD8+ TILs within the epithelial component of OCs has been associated with favorable prognosis, but the investigators note "prior analyses have been inadequately powered to evaluate histotype-specific survival associations."

To fill this evidence gap, the team prospectively followed more than 5,500 women with OC (mean age at diagnosis, 58), including 3,196 with high-grade serous ovarian carcinomas (HGSOCs). The four other OC histotypes studied were low-grade serous, endometrioid, mucinous, and clear-cell. Follow-up lasted nearly 25,000 person-years.

Among the five histotypes, HGSOCs were associated with the greatest TIL infiltration. For women with HGSOCs, increasing CD+ TIL levels were significantly associated with longer overall survival: median survival of 2.8 years when patients had no CD8+ TILs, 3.0 years with low CD8+ TIL levels, 3.8 years with medium levels, and 5.1 years with high levels.

The authors note that women with high CD8+ TIL levels had a 43% lower risk of death compared to women with no evidence of CD8+ TILs. The benefit of higher CD8+ TIL persisted regardless of the extent of residual disease after cytoreduction and germline BRCA1 mutation, but not for carriers of the BRCA2 mutation.

Higher CD8+ TILs also showed a trend toward survival benefit in women with endometrioid OC and, possibly, even in the small group of participants with mucinous carcinomas. No benefit was found for the other OC histotypes.

Given these findings, the researchers conclude, "A clinically applicable scoring system for CD8+ TILs should be developed to incorporate into clinical trials."

In an email to Reuters Health, Dr. Block said, “This study demonstrates that if a patient with ovarian cancer has a high number of (CD8+ TILs) . . . that patient has a better prognosis than patients with fewer CD8+ TILs. This finding is true for several types of ovarian cancer, but not all types. . . . Efforts to understand which factors lead to increases in CD8+ TILs are underway, so that we can use this knowledge to try to improve patient outcomes."

Gynecologic oncologist Dr. John H. Farley of the University of Arizona Cancer Center at Dignity Health Saint Joseph, Phoenix, told Reuters Health by email, "This is the largest report on intraepithelial CD8+ TILs in ovarian cancer to date - and shows a robust increase in survival for increasing TIL levels in women with high-grade serous ovarian cancer."

Dr. Farley, who was not involved in the study, added, "The quantity of CD8+ TILs is important, and the most immune-rich HGSOCs are the most likely to have improved clinical outcome. Because there are fewer than a handful of other validated prognostic biomarkers for HGSOCs, these results may provide an additional prognostic marker."

SOURCE: http://bit.ly/2kTpB1h

JAMA Oncol 2017.