Chemotherapy with Immune Checkpoint Blockade Shows Better Tumor Response

Researchers have found that chemotherapy drugs can better respond to cancerous cells with the help of an immune checkpoint blockade, a promising form of therapy.

"Immune checkpoint blockade has revolutionized cancer therapy because it can durably control tumor progression, even in patients who fail to respond to other treatments," said senior author Mikael Pittet, PhD. "But the drawback is that it only benefits a fraction of patients. We have found a way to make unresponsive lung tumors sensitive to checkpoint blockade immunotherapy and achieve long-lasting control of tumor growth in these animal models."

Tumors activate checkpoints — molecules that suppress the activity of cytotoxic T cells (CTLs) – to evade the immune system.

Previous trials that explored blocking immune checkpoints have shown long-term control of different types of cancer, but this was only among a minority of people. Data suggests that patients who have tumors with CTLs have greater benefit.

The study tested different combinations of FDA-approved chemotherapy drugs on lung cancer mouse models to determine whether or not it could induce CTL infiltration in tumors. The results of the study showed that oxaliplatin and cyclophosphamide (Oxa-Cyc) was the only combination that could do this.

Mice treated with only the Oxa-Cyc had tumors that grew at a slower pace. The Oxa-Cyc was able to stimulate the increased activity of the immune system in the tumor. This was needed in addition to CTL infiltration in order to control the tumor.

It was also found that when Oxa-Cyc was combined with the immune checkpoint blockade, it could control the tumor growth in lung cancer mouse models. This is something that was not possible when used individually.

Furthermore, when testing other chemotherapy drugs in combination with immune checkpoint therapies, researchers found that other cancer types had a delayed progression in tumor growth as well.

"The genetic mouse model of lung cancer used in this study is notoriously resistant to today's cancer treatments, in contrast to many other models that are sensitive to several chemotherapy agents," Pittet said. "We hope this model replicates treatment-resistant disease enough so that our findings can be translated to patients, but clinical trials are needed to examine whether that will be the case. Since the drugs shown to work in this study are all FDA-approved, the combination could be quickly tested in patients with lung cancer. We also plan to explore whether precision medicine approaches, which could identify drugs that best promote tumor infiltration by CTLs in a given patient, could extend the benefits of checkpoint blockade to even more patients."