TIL Levels Predict High-Grade Serous Ovarian Carcinoma OS

A large collaborative analysis of women with major invasive epithelial ovarian cancer shows a relationship between tumour-infiltrating lymphocyte count and outcome of high-grade serous disease

medwireNews: For women with high-grade serous ovarian carcinomas (HGSOCs), high levels of CD8+ tumour-infiltrating lymphocytes (TILs) are significantly and independently associated with improved overall survival (OS), research reveals.

The Ovarian Tumor Tissue Analysis (OTTA) Consortium collated immunohistochemical findings from 5078 patients with one of five major invasive histotypes of epithelial ovarian cancer who were followed up for over 24,000 person–years, including 3196 women with HGSOCs.

Median OS was 5.1 years for patients with HGSOC and a high CD8+ TIL count, defined as at least 20 cells per high-powered field examining the epithelial components of tumour islets. This was significantly longer than the median OS of 2.8, 3.0 and 3.8 years for women with no, low (1–2) or moderate (3–19) CD8+ TILs per high-powered field, respectively.

After adjusting for study, age and disease stage, improved OS with a high CD8+ TIL count was detected in patients with and without macroscopic residual disease after primary cytoreduction (hazard ratio [HR]=0.64 and 0.51 versus no CD8+ TILs, respectively), and in patients who had received a standard first-line chemotherapy regimen (HR=0.52).

In addition, women with germline BRCA1 mutations were significantly more likely to have a high CD8+ TIL count than BRCA2 mutation carriers and women without any BRCA mutation, although a high CD8+ TIL level was only significantly prognostic for BRCA1 and noncarriers, with HRs of 0.27 and 0.46 versus no CD8+ TILs, respectively.

A survival benefit with high levels of CD8+ TILs was also detected for women with endometrioid and mucinous OCs but not for those with low-grade serous or clear cell OCs, report Ellen Goode, from the Mayo Clinic in Rochester, Minnesota, USA, and colleagues.

“This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival”, they write in JAMA Oncology.

“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.”

And the OTTA investigators recommend: “A clinically applicable scoring system for CD8+ TILs should be developed to incorporate into clinical trials.”


Ovarian Tumor Tissue Analysis (OTTA) Consortium. Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer. JAMA Oncol; Advance online publication 12 October 2017. doi:10.1001/jamaoncol.2017.3290

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