Cells in our immune system are best known for providing security against external invaders such as bacteria and viruses. These immune cells also guard against internal threats, including cancerous tumors.
Different forms of cancer cells and tumors have their own tricks for avoiding detection by the body’s security system altogether or otherwise sabotaging any attempts to muster an immune response. In the case of the most common and difficult-to-treat form of ovarian cancer, this ability to suppress the immune system also makes the cancer resistant to treatments known as immunotherapies that seek to supercharge immune cells.
“Even if you boost the capability of immune cells, a treatment will have limited success if the cells struggle to recognize and react to the tumor,” said David Schlaepfer, PhD , a professor in the department of OBGYN and Reproductive Sciences at the University of California San Diego Moores Cancer Center.
Scientists at Sanford Burnham Prebys and the University of California San Diego published findings February 25, 2026, in Cell Reports demonstrating a treatment approach in mice that allowed more tumor-fighting cells to approach tumors, shifted the behavior of other immune cells to work against tumors, and made immunotherapy more effective. The research team also uncovered what cellular changes prompted the immune system to better pierce the tumors’ veil of immunosuppression.
Prior research had pointed to a culprit inside ovarian cancer cells that helped protect them from the immune system. Genetic mutations cause an overabundance of the focal adhesion kinase (FAK) protein in more than three out of four cases of high grade serous ovarian cancer and is linked with reduced patient survival.
In addition to patients without these mutations tending to fare better, preclinical studies pairing FAK-blocking drugs with chemotherapy have had encouraging results leading to an active Phase II clinical trial . These observations suggest that FAK helps safeguard tumors. And that these safeguards could be circumvented to give chemotherapy and/or immunotherapy a boost.
To better understand the potential of blocking FAK in this disease, the scientists turned to an aggressive, chemotherapy-resistant ovarian mouse tumor model that has mutations comparable to high grade serous ovarian cancer. The team compared conditions in these mice after using a drug to block FAK in various combinations with chemotherapy and immunotherapy so that each grouping could be evaluated against each other and a control group that received no treatment.
Researchers assessed the levels of tumor-fighting immune cells called B and T cells, tumor size and days of survival. Combining the FAK-blocking drug with both chemotherapy and immunotherapy achieved the best effects on immune cell recruitment, tumor size reduction and survival time.
“Once it was established that genetically or pharmacologically targeting FAK improved the ability of the immune system to recognize and attack ovarian tumor models, then we needed to figure out how this worked,” said Kevin Tharp, PhD , an assistant professor in the NCI-designated Cancer Center’s Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys Medical Discovery Institute.
The team narrowed in on immune cells called macrophages. Rather than focusing on their more widely recognized function of swallowing up and digesting bacteria, viruses and other hazards, the investigators saw that inhibiting FAK changed chemical signals sent by macrophages to communicate with other immune cells.
“With FAK blocked, the macrophages that coordinate the immune system’s response to a tumor started assisting other immune cells in recognizing and targeting the tumor,” Tharp, second author of the study.
The scientists showed that macrophages’ revitalized coordination efforts were due to the cells broadcasting a chemical signaling protein called CXCL13. Using their rediscovered megaphones, the macrophages recruited B and T cells to build what is akin to forward operating bases against the tumor known as tertiary lymphoid structures.
The authors say that further research is needed to set the stage for potential clinical trials of combination therapies using FAK inhibitors, chemotherapies and immunotherapies.
“The moment high grade serous ovarian cancer becomes metastatic, it's too distributed throughout the body for you to really do anything but recruit the immune system,” said Tharp.
“I think that this represents an important treatment opportunity for patients who have progressed and not responded to the standard of care. It's an extreme clinical need.”
Tharp emphasized the importance of combining expertise among multiple labs to make this research possible.
“I’m grateful to have found such a welcoming and supportive collaborator in David Schlaepfer, and it also speaks the collaborative nature of science in San Diego where we work across institutions on the shared mission of studying cancer to find better treatments.” Schlaepfer is the senior and corresponding author of the manuscript.
Xiao Lei Chen, MS, a staff research associate III at the University of California San Diego, is first author of the publication.
Additional authors include:
The study was supported by the National Institutes of Health, National Cancer Institute, National Science Foundation, V Foundation and Sigrid Juselius Foundation.
The study’s DOI is 10.1016/j.celrep.2026.117009 .
Cell Reports
Experimental study
Animals
FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages
24-Feb-2026
Stupack is a consultant for Amplia Therapeutics Limited. All other authors declare that they have no conflicts of interest.