Increased CD8+ TIL Counts Linked to Prolonged Survival in Patients With Certain Ovarian Cancers

Epithelial ovarian cancer (OC) is responsible for 14,000 deaths each year in the United States, and although initial remission is often achieved, patients often relapse and succumb to the disease. Increasing CD8⁺ tumor-infiltrating lymphocytes (TILs) in several ovarian cancer histotypes is associated with an increased rate of survival, according to a study published in JAMA Oncology.

“Cytotoxic CD8⁺ TILs participate in immune control of epithelial ovarian cancer,” wrote the authors of the study. “However, little is known about prognostic patterns of CD8⁺ TILs by histotype and in relation to other clinical factors.”

The authors assessed a prospective cohort of 5577 women with a primary diagnosis of epithelial ovarian, peritoneal, or fallopian tube cancer. Of the 5577 women, 5078 had tumors of the 5 major histotypes: high-grade serous OC (HGSOC), endometrioid OC (ENOC), clear cell OC (CCOC), mucinous OC (MOC), and low-grade serous OC (LGSOC). The patients were followed until death from any cause. Tumor specimens were taken from an initial debulking surgery, formalin fixed, paraffin embedded, and arranged on tissue microarrays.

Epithelial CD8⁺ TILs were examined using a 4-tiered scoring system. Of the HGSOC cases, 83% had evidence of CD8⁺ TILs with lower rates seen in LGSOC (73%), ENOC (72%), CCOC (52%), and MOC (51%).

The results showed a strong association between increasing levels of CD8⁺ TILs and prolonged survival in HGSOC cases. The median survival was 2.8 years for women negative for CD8⁺ TILs, 3 years for low levels, 3.8 years for moderate levels, and 5.1 years for high levels. According to the authors, at the extremes, women with high levels of CD8⁺ TILs had a 43% reduced risk of death compared to women negative for CD8⁺ TILs.

Increasing levels of CD8⁺ TILs were also linked to prolonged survival for women with ENOC and MOC.

Among HGSOCs, CD8⁺ TILs were favorable regardless of the extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation. However, they were not prognostic for BRCA2 mutation carriers.

“These large-scale analyses show that CD8⁺ TILs vary by histotype with HGSOC tumors having the highest levels and a strong association with survival, regardless of extent of residual disease or first-line chemotherapy treatment,” wrote the authors. They continued, “We showed for the first time that CD8⁺ TILs in HGSOC cases with germline BRCA2 mutations may not be associated with survival. Finally, we found that ENOC and MOC tumors show trends associating CD8⁺ TILs with survival time and that CCOC do not show these trends.”

The authors indicated that a clinically applicable scoring system for CD8⁺ TILs should be developed and incorporated into clinical trials.