Harnessing the Immune System to Advance Cervical Cancer Treatment

The strong focus on screening and vaccination has transformed cervical cancer prevention–but has also left a critical gap in effective therapies for patients who require intensive treatment and continue to face poor outcomes.

Research led by W. Martin Kast, PhD, aims to address this gap. A former Cancer Research Institute (CRI) Clinic and Laboratory Integration Program (CLIP) fellow, Dr. Kast’s research focuses on how the immune system responds to standard cervical cancer treatment and how immunotherapy can strengthen those responses. His work highlights new ways the immune system may be harnessed to create longer-lasting protection against cervical cancer.

Why Cervical Cancer is Unique

Over 90% of cervical cancer is caused by human papillomavirus (HPV). This unique viral feature is the reason cervical cancer vaccines, like Gardasil®, are so effective at preventing cancer development. 

Prevention Matters! 
Most cervical cancers can be prevented through HPV vaccination and regular screening. Together, these tools offer powerful protection: vaccination guards against the HPV types responsible for most cases, while screening can detect precancerous changes early–often before cancer ever develops.

While HPV makes cervical cancer more visible to the immune system, it also makes it more challenging to treat than traditional cancers.

HPV causes cancer by producing two viral proteins that drive cell growth. Importantly, these proteins are not found in healthy cells, making them ideal targets for immunotherapies that help the immune system recognize and destroy cancer cells.

Viruses evolve to “outsmart” the immune system to avoid detection, and HPV is no different. The virus can suppress early immune responses, allowing infection to persist for years before cancer develops. Tumor development adds another layer of immune suppression by creating an environment that makes it difficult for immune cells to enter the tumor or stay active long enough to eliminate it.

Cervical cancer has something rare: truly tumor-specific targets. If you train the immune system to recognize them, it can attack cancer cells without harming healthy tissue.

Learning From Standard Treatment

Dr. Kast’s CRI-funded research examined how the standard treatment of chemotherapy and radiation (chemoradiation) affects the immune system, uncovering opportunities to enhance long-term antitumor responses.

His team discovered that while chemoradiation temporarily activates immune cells, it also increases signals linked to immune exhaustion, which can make the immune system less effective at identifying and fighting cancer cells. This insight helped explain why immunotherapy drugs known as immune checkpoint inhibitors (ICIs) targeting these markers can be effective when given after chemoradiation. By inhibiting the markers of exhaustion, ICIs essentially “take the brakes” off the immune system and allow it to find and attack cancer cells.

Support from CRI enabled Dr. Kast’s team to conduct in-depth immune studies within national clinical trials, helping connect benchside discoveries to bedside patient care. These findings contributed to a transformative shift in cervical cancer treatment: today, immunotherapy with checkpoint inhibitors is part of the standard treatment approach for many patients with advanced disease.

What we learned is that standard treatment doesn’t just kill cancer cells–it reshapes the immune system. Understanding that helped point directly to the next treatment step.

Overcoming the Barriers

Despite tremendous progress in cervical cancer treatment, the work is not yet done. HPV’s ability to evade immune detection, combined with the immune-suppressive tumor environment, can limit the effectiveness of immunotherapy in different patients.

Ongoing work in the field aims to understand why patient responses to immunotherapy can vary and how to extend these benefits to more people. Researchers are exploring strategies with approaches like combining different immunotherapies and developing therapeutic cancer vaccines designed to train immune cells to recognize HPV-driven tumors. Other researchers, like Dr. Kast, are uncovering new immune pathways that may be blocking effective responses in advanced disease–offering potential new targets for future therapies.

Looking Ahead

The future of cervical cancer treatment will likely involve smarter, more personalized combinations of therapies. Immunotherapy is already part of standard care for some cervical cancers, and advances in therapeutic vaccines, immune biomarkers, and combination approaches continue to move the field forward.

For patients and loved ones, the message is one of optimism: Today’s discoveries are shaping tomorrow’s treatments–offering renewed hope for patients with cervical cancer.