Hamanishi and colleagues first reported that high expression of PD-L1 on ovarian cancer cells was associated with poorer outcomes.3
The 5-year survival rate for patients with high- versus low-expressing PD-L1 tumors was 52.6 ± 7.7% versus 80.2 ± 8.9% (P
= .016), respectively. PD-L2 expression was also associated with poorer outcomes, but that was not statistically significant. High expression of PD-L1 on ovarian cancer cells was associated with reduced infiltration of cytotoxic T lymphocytes into tumors, suggesting that PD-L1 expression promotes an immunosuppressive microenvironment by inhibiting T-cell infiltration. Both PD-L1 expression and TIL were independent prognostic factors, although PD-L1 expression was inversely correlated with survival. In preclinical models, PD-L1 expression can be induced by interferon gamma (often produced by TILs) and administration of chemotherapy, suggesting a balance that maintains an immune suppressive environment. PD-1/ PD-L1 blockade causes regression of ovarian tumors in a syngeneic ovarian cancer mouse model, further validating the importance of this regulatory pathway.
PD-L1 expression is not limited to tumor cells and has been reported on immune cells including antigen-presenting cells, T cells, and B cells. A recent study showed that PD-L1 expression is predominantly expressed by macrophages in ovarian cancer rather than on the ovarian cancer cells themselves; in this context, macrophage-associated PD-L1 expression was a marker of favorable prognosis. The differences between this study and the one above may be due to the differences in the antibodies used, but they reflect the developing understanding of PD-L1 expression and its prognostic role in ovarian cancer. PD-L1 expression may be a marker of a tumor poised to respond to immune stimulatory effects of chemotherapy; or, perhaps because PD-L1 may suppress the activity of immune-suppressive immune cells (ie, Tregs), PD-L1 expression on immune cells could tip the balance toward a more favorable immune microenvironment. Thus, evaluating PD-L1 expression on tumor cells in isolation is not sufficient to predict immune response and efficacy of immune checkpoint blockade in ovarian cancerBradley J. Monk, MD, practices with Arizona Oncology and is a professor of gynecologic oncology at the University of Arizona and Creighton University, Phoenix, Arizona. At the 35th annual CFS®, Monk discussed the role of immunotherapy in ovarian cancer.
- Teng MW, Khanna R, Smyth MJ. Checkpoint immunotherapy: picking a winner. Cancer Discov. 2016;6(8):818-820. doi: 10.1158/2159-8290.CD-16-0694.
- Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003:348(3):203-213. doi: 10.1056/NEJMoa020177.
- Hamanishi J, Mandai M, Ikeda T, et al. Safety and antitumor activity of anti–PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33(34):4015-4022. doi: 10.1200/JCO.2015.62.3397.