Although this treatment has been demonstrated to be quite helpful in many cancers, it has performed poorly in ovarian cancer, with only approximately 10% of patients benefiting.
Immunotherapy has ushered in a new era in cancer treatment. Checkpoint inhibitors are a type of cancer treatment that supports the immune system’s T cells in recognizing and attacking cancers, although they aren’t successful in all malignancies.
In a mouse model of ovarian cancer, a study published today in “Science Advances” demonstrates how particular cells cause immunotherapy resistance and how blocking a signaling pathway in these cells improves tumor responses to immunotherapy.
Immunotherapy can be effective for individuals with melanoma, head and neck cancer, and lung cancer, among other cancers.
Immunotherapy, on the other hand, has had mixed results in ovarian cancer: only around 10% of patients benefit, and the benefit is typically less substantial than in other tumor types. The purpose of this study was to figure out why ovarian cancer is resistant to immunotherapy and see if we could come up with novel ways to improve immunotherapy’s effectiveness.
Ovarian cancer is a serious disease. It is the leading cause of death from malignant tumors in the Western world. In United States, more than 21,750 cases are diagnosed each year, which represents just over 2.5% of cancers among women, behind colorectal and uterine body cancers. It usually occurs between the ages of 50 and 75, postmenopausal, although younger women can also suffer from it.
The study authors explain that this work shows that healthy non-cancerous cells, known as mesenchymal stem cells (MSCs), under the influence of cancer cells, “create a barrier that prevents immune cells from entering the tumor.” This is what is called “tumor immune exclusion” in cancer.
In addition, they add, MSCs “recruit and promote the generation of other immunosuppressive cells to inactivate any immune cells that can penetrate the barrier.” This combination, Senior author Ronald Buckanovich explains, “prevents immune cells from doing their jobs and killing cancer cells, even in the presence of immune-stimulating therapy.”
In short, “if you can’t get to work, you can’t do your job.”
But our research shows that inhibiting a signaling pathway, known as the hedgehog pathway, “prevent MSCs from establishing the immune barrier and reverse tumor immune exclusion. Importantly, we showed that clinically available hedgehog pathway inhibitors could restore the activity of immune therapy in otherwise immunotherapy-resistant ovarian cancer models.”
According to the researcher, these findings have several important clinical implications. First, it “strongly implicates MSCs as an important therapeutic target for immune therapy in ovarian cancer patients. Furthermore, we identified other potential therapeutic targets that could be contributing to immunosuppression in ovarian cancer patients. One protein— the TGF beta-induced protein — was found to predict a poor response to immunotherapy. We are currently developing new therapies targeting this protein.”
Buckanovich anticipates that a clinical trial is already planned for patients with ovarian cancer.
“In partnership with Genentech, which will provide the hedgehog inhibitor and immunotherapy agent, we plan to launch a new clinical trial to determine if a hedgehog inhibitor can improve the benefits of immunotherapy in patients with therapy-resistant ovarian cancer.”
Remember that these are patients who “have few treatment options.”
The investigator is hopeful that this approach may have significant benefits for these patients.
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