Women with metastatic ovarian cancer treated with chemotherapy prior to surgery have higher levels of specific immune cells with the ability to attack tumor cells. These findings suggest that immunotherapy designed to remove the breaks of immune cells may be used in these patients to enhance anti-tumor responses and improve disease control.
The study, titled “Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma“, was published in Clinical Cancer Research, and developed by researchers at the Queen Mary University of London, in the U.K.
“We are studying a type of ovarian cancer called high-grade serous ovarian cancer (HGSC), which is quite difficult to treat for two main reasons: first, it is often detected after it has spread quite extensively in the body; and second, although the disease can respond well to the first chemotherapy treatments, it often relapses and becomes more difficult to treat,” Frances R. Balkwill, PhD, professor of cancer biology at Barts Cancer Institute in Queen Mary University of London, United Kingdom, said in a press release. Therefore we need to find other treatment options after the initial treatment is given.”
Previous research has shown that chemotherapy can have a dual role in fighting some tumors, inducing both tumor cell death and stimulating the expansion and activation of anti-tumor immune cells. Now, the researchers wanted to address whether this was also true for women with ovarian cancer.
They examined biopsies and blood samples from 54 women with advanced stage HGSC before and after receiving platinum-based chemotherapy prior to surgery, and from six patients who underwent surgery without prior chemotherapy. Patients were categorized into minimal responders, poor responders, and good responders, depending on their progression-free survival and overall survival.
Results revealed that patients who received chemotherapy had increased activation of tumor killing T-cells, whereas a particular subset of T-cells, called regulatory T cells, that inhibit immune system activity were decreased. These results were particularly more pronounced in the ‘good responders’ group.
Nonetheless, the investigators found that anti-tumor T-cells had either the same or increased levels of PD-L1, a protein that acts as an immune checkpoint and hampers an efficient immune response. Targeting this pathway with commonly used immunotherapies, such as nivolumab (Opdivo) or pembrolizumab (Keytruda) could improve chemotherapeutic effects.
The team also found that chemotherapy reduced blood levels of certain proteins involved in tumor growth. “This could help immunotherapies work better,” Balkwill noted. “The chemotherapies, carboplatin and paclitaxel, given in our study are also used to treat many different cancer types. It will, therefore, be very interesting and potentially promising if similar effects are seen in other cancer types, such as lung cancer,” she added.
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