Tackling inflammation improves the effectiveness of cancer immunotherapy

Cancer immunotherapy is one of the treatment options for the disease, but not all patients respond to the most commonly used type of drug, called immune checkpoint inhibitors (ICIs).

Now, researchers at the Abramson Family Cancer Research Institute at the University of Pennsylvania have observed in a small clinical trial that adding Janus kinase (JAK) inhibitors, which prevent inflammation from within cellsmay improve the antitumor response of immunotherapy by ICI anti-PD-1 (programmed death protein) in patients with advanced lung cancer.

According to what he told SINC Andy Minnco-lead author of the study and director of the institution’s Center for Immunotherapy, “the result builds on a growing body of evidence about dual nature of inflammation“This may be useful against infectious pathogens and cancer in the short term, but can also lead to a weakened immune system when the disease becomes chronic.”

The addition of Janus kinase (JAK) inhibitors, which prevent inflammation from within cells, may improve the antitumor responses of anti-PD-1 ICI immunotherapy.

Patients receiving cancer immunotherapy “often show signs of this chronic inflammatory response, especially a cytokine called interferonwhich is associated with worse outcomes,” Minn explains.

In the study, the researchers used a JAK1 inhibitor to reduce persistent inflammatory signaling without interfering with the initial inflammatory signaling required to generate antitumor activity.

Study on 21 patients with lung cancer

This inhibitor was given for six weeks to 21 patients with advanced non-small cell lung cancer, but only after they received two doses of anti-PD1 immunotherapyThe result was an overall response rate of 67% and a median progression-free survival of almost 24 months, which are very high rates for this type of tumor.

“Combining a JAK inhibitor with immunotherapy may seem surprising to many oncologists, since the emphasis is typically on generating a strong inflammatory response for anti-PD1 treatment to be effective.”

However, he adds, “it is becoming increasingly clear that chronic inflammation, particularly chronic inflammation caused by interferon, can be harmful. The high response rate in the study and the improvement in immune cell health suggest that our approach may help. control inflammation and interferon levels before they become harmful.”

The result was an overall response rate of 67% and a median progression-free survival of nearly 24 months.

The authors point out that although the study did not include a comparison group, “the results show the surprising efficacy of the combination with JAK1 anti-inflammatory agents.”

In this sense, they explain that “response rates using the anti-PD-1 checkpoint inhibitor drug pembrolizumab alone in large clinical trials for stage 4 lung cancer are typically approximately 45% and were as high as 67% in our study,” they explain. They. insist. “Even now, a significant proportion of patients are still alive, suggesting that many of these reactions are long-lasting.”

Patient analyses and earlier tests in mouse models of advanced lung cancer confirmed the treatment’s effectiveness.

More extensive research

Andy Minn tells SINC what the team now plans to do

Larger randomized clinical trials to establish that the addition of a JAK inhibitor improves immunotherapy against advanced lung cancer.

The high response rate and improvement in immune cell health suggest that our approach may help control inflammation and interferon levels before they become harmful.

Andy Minn
— Co-author of the study (University of Pennsylvania)

“We also want to explore other cancer types and clinical scenarios where the same strategy might be effective. An example would be people who relapsed after anti-PD1 therapy. Finally, although the response rates in our study were high and promising, we are interested in learning why some patients did not respond and how to use JAK anti-inflammatory agents to extend the possible benefit to these patients as well,” the expert concludes.

Link: D. Matthew and others- “Combined JAK inhibition and PD-1 immunotherapy in patients with non-small cell lung cancer.” Journal The science, 2024 | DOI: 10.1126/science.adf1329.