“The immune system may be an under-recognized contributor to the tumor response to chemotherapy,” said researcher Philip H. Abbosh, MD, PhD.
Neoadjuvant chemotherapy used to treat muscle-invasive localized bladder cancer appears to do more than damage cancer cells. The chemo might also harness the immune system to search for and destroy bladder cancer cells, researchers reported at the American Association for Cancer Research annual meeting in Washington.
“The immune system may be an under-recognized contributor to the tumor response to chemotherapy,” according to lead author Philip H. Abbosh, MD, PhD, of Fox Chase Cancer Center, Philadelphia.
Dr. Abbosh and colleagues performed whole exome sequencing and gene expression analyses on three cohorts of patients who had cisplatin-based neoadjuvant chemotherapy.
“We found that tumors with a high mutation burden had a high neoantigen load. Neoantigens are the tumor-associated peptides that can be recognized by the immune system. Responding tumors also had a high CD8 T cell infiltrate signature, suggesting that they were recognizing the neoantigens but were ‘indifferent.’ The last piece of data is very preliminary, but suggests that the PD1 checkpoint may have a role in chemo response. It’s not clear yet if it is a cause or consequence of response, or if it is an epiphenomenon,” Dr. Abbosh told Urology Times.
These findings are, in part, novel, according to Dr. Abbosh.
“I am not aware of other research showing that chemotherapy response is mediated by T cell recognition of the tumor, but there is definitely research showing that chemotherapy does activate an anti-tumor immune response in other ways,” he said.
As for what this study says about chemotherapy versus immunotherapy for bladder cancer treatment, Dr. Abbosh said it’s not clear. Immunotherapy trials clearly show immunotherapy has an effect in patients who failed chemotherapy, but there may be some patients who respond to both, and, therefore, only need either immunotherapy or chemo or need both treatments. That’s speculation, for now, he said.
The hope from the current findings is to develop a deliberate approach for combining chemo and immunotherapy in bladder cancer.
“We may get to a point where we combine chemo with a vaccine or adoptive therapy, for instance, to enhance response or even potentially treat metastatic disease. These patients all had clinically localized bladder cancer, so they underwent curative-intent surgery,” Dr. Abbosh said.
The next step the authors plan to take is to look more closely at what T cells are and aren’t doing and which subsets are contributing to the response.
“We are also looking at what is going on in the lymph nodes adjacent to the bladder. That is probably where business takes place,” Dr. Abbosh said.
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