Dr Cannon on Improving Responses With Immunotherapy in Ovarian Cancer

Martin Cannon, PhD, professor, Department of Microbiology, University of Arkansas for Medical Sciences College of Medicine, discusses potential reasons that contribute to the lack of success with immune checkpoint inhibitors in ovarian cancer, highlighting areas to focus upon to improve these responses to immunotherapy approaches in the future.

immune checkpoint inhibitors have produced encouraging therapeutic responses in patients who have presented with a wide spectrum of tumor types, Cannon begins. However, the agents use in ovarian cancer has proven far less effective, he says.

When attempting to understand why immunotherapy has not yielded high responses in ovarian cancer, it is first vital to recognize that immune checkpoint inhibitors target T-cell responses rather than the tumor itself, Cannon states. Consequently, the utilization of immune checkpoint inhibitors becomes ineffective in the absence of an initial intrinsic T-cell response to the tumor, he explains. This lack of substantial T-cell activation could be present in ovarian cancer, and may be attributed to factors such as a low tumor mutational burden or a low number of T-cell stimulating antigens, Cannon says, leading to limited immunogenicity. Immune suppression in the tumor microenvironment may also occur due to the presence of regulatory T-cells, he adds. These features decrease the efficacy of immune checkpoint inhibitors, such as pembrolizumab (Keytruda) and nivolumab (Opdivo), necessitating upfront intervention prior to their use, Cannon notes.

To improve the functionality of these drugs, it is important to address the initiation of anti-tumor T-cell immunity as well as local immune suppression, Cannon continues. An optimal approach, therefore, involves stimulating anti-tumor T-cell immunity and concurrently mitigating immunosuppression within the tumor microenvironment, he suggests.

If anti-tumor T-cell responses can be proactively enhanced, meaningful responses to immune checkpoint inhibitors in ovarian cancer may become attainable, Cannon says. This comprehensive strategy offers a promising direction for improving the landscape of ovarian cancer treatment, Cannon concludes.