Combining Chemotherapy With Immunotherapy may be Effective Against Ovarian Cancer

Ovarian cancer is often diagnosed at late stages, so chemotherapy is a key part of treatment. Most patients will respond to it at first, but everybody develops chemoresistance. And that is when ovarian cancer becomes deadly.

Inside each ovarian tumor, there are good cells and bad cells. A new study reported in Cell explains their roles: - The bad cells are fibroblasts. They work to block chemotherapy, which is why nearly every woman with ovarian cancer becomes resistant to treatment.

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Ovarian cancer affects both the ovaries and is referred to as the 'silent killer' as the symptoms go unnoticed until the disease advances.

‘The good cells in ovarian tumor are immune T cells that can reverse resistance to chemotherapy. This suggests the potential to harness immunotherapy drugs to treat ovarian cancer.’

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- The good cells are immune T cells. They can reverse that resistance.

These findings suggest a whole different way of thinking about chemotherapy resistance - and the potential to harness immunotherapy drugs to treat ovarian cancer.

Study author J. Rebecca Liu, associate professor of obstetrics and gynecology at the University of Michigan, said, "In the past, we've thought the resistance was caused by genetic changes in tumor cells. But we found that's not the whole story."

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Researchers looked at tissue samples from ovarian cancer patients. They separated the cells by type to study the tumor microenvironment in cells and in mice. They also linked their findings back to actual patient outcomes.

Ovarian cancer is typically treated with cisplatin, a platinum-based chemotherapy. The researchers found that fibroblasts blocked platinum. These cells prevented platinum from accumulating in the tumor and protected tumor cells from being killed off by cisplatin.

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Ovarian cancer readily spreads to abdominal organs, which are covered by a layer of cells called the mesothelium and less than half of the women diagnosed with ovarian cancer will survive beyond 5 years.

Immune T cells, on the other hand, overruled the protection of the fibroblasts. When researchers added the immune T cells to the fibroblasts, the tumor cells began to die off.

"T cells are the soldiers of the immune system. We already know that if you have a lot of T cells in a tumor, you have better outcomes. Now we see that the immune system can also impact chemotherapy resistance," says study author Weiping Zou, Charles B. de Nancrede Professor of Surgery, Immunology and Biology at the University of Michigan.

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Circulating tumor cells spread ovarian cancer through the bloodstream, homing in on a sheath of abdominal fatty tissue where it can grow and metastasize to other organs.

By boosting the immune T cells, the researchers were able to overcome the chemotherapy resistance in mouse models. They used interferon, a type of small protein, to manipulate the pathways involved in cisplatin.

The researchers suggest that combining chemotherapy with immunotherapy may be effective against ovarian cancer. PD-L1 and PD-1 pathway blockers are FDA-approved treatments in some cancers, although not ovarian cancer.

"We can imagine re-educating the fibroblasts and tumor cells with immune T cells after chemoresistance develops," Zou says.

"Then we could potentially go back to the same chemotherapy drug that we thought the patient was resistant to. Only now we have reversed that and it's effective again," Liu adds.

Source-Eurekalert