Hae Lin Jang, PhD

A recent study describes a promising new approach to cancer treatment that works differently from most current immunotherapy treatments. Instead of focusing on T cells, it activates B cells—an important but often overlooked type of immune cell—to help the immune system recognize and destroy hard-to-treat “cold” tumors.

A research team led by Mass General Brigham’s Shiladitya Sengupta, PhD, and Hae Lin Jang, PhD, discovered CMTR2 as a new target for cancer immunotherapy and developed the first small molecule CMTR2 inhibitor, AT-1965.

One of the biggest challenges in cancer treatment is that tumors can hide from the immune system. CMTR2 helps cells label their RNA as “self,” signaling that they belong in the body and should not be attacked. The researchers found that inhibiting CMTR2 makes cancer cells appear “virus-like”, helping the immune system to recognize and eliminate them. This triggers a powerful antiviral immune response against the tumor.

Shiladitya Sengupta, PhD

In preclinical studies, AT-1965 recruited B cells and other anti-tumor immune cells, converted immune-cold tumors into immune-hot tumors, caused strong tumor regression, and generated long-lasting immune memory that helped prevent cancer recurrence. Importantly, the anti-tumor effect depended on B cells, highlighting a previously underappreciated role for these immune cells in cancer immunotherapy.

Analysis of human cancer data showed that patients with higher levels of B cells in their tumors had better survival rates while patients with higher CMTR2 expression had worse outcomes, which suggests that this treatment approach could open up a new frontier in immuno-oncology.

Mass General Brigham’s Heena Aggarwal, PhD, is one of five first authors on the study.

Summary reviewed by Shiladitya Sengupta, PhD and Hae Lin Jang, PhD.

Published in Nature Neurotechnology on June 12, 2026| Read the paper: “Activating B Cell Immune Response Regresses Immunologically Cold Tumours”