Innovative Bladder Cancer Therapy Reprograms Bone Marrow to Enhance Immune Response

A groundbreaking study by researchers at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center (MSK) reveals that bladder cancer treatment with Bacillus Calmette-Guérin (BCG) not only stimulates a local immune response but also induces systemic immunological changes by reprogramming the bone marrow. BCG, a weakened form of Mycobacterium bovis, has long been used as a frontline immunotherapy for early-stage bladder cancer. Traditionally thought to act mainly at the tumor site by enhancing T cell activity, new evidence suggests that BCG's effects extend deeper into the body's immune system.

The research demonstrates that BCG travels from the bladder to the bone marrow, influencing the production of immune cells called myeloid cells. This process primes the innate immune system, enabling it to respond more effectively to cancer cells and other threats. Using advanced analytical techniques like Progenitor Input Enrichment sequencing (PIE-seq), scientists studied gene activity in blood samples from bladder cancer patients treated with BCG, discovering significant changes in stem cell programming in the bone marrow.

Notably, the study shows that the reprogrammed stem cells generate more potent immune cells capable of attacking tumors. Additionally, combining BCG with checkpoint inhibitors—a type of immunotherapy that boosts T cell activity—resulted in more effective tumor suppression and increased survival in mouse models. This synergy indicates potential for enhancing current cancer treatments by harnessing innate immunity.

The findings broaden the understanding of BCG's anti-cancer mechanisms, highlighting its capacity to shape systemic immune responses beyond the bladder. The research also opens pathways for developing strategies that stimulate immune cell reprogramming to improve immunotherapy outcomes across various cancer types.

This work underscores the importance of innate immune system training in cancer therapy and suggests that leveraging bone marrow reprogramming could augment existing immunotherapies, paving the way for more effective treatment protocols.

Source: https://medicalxpress.com/news/2025-05-bladder-cancer-treatment-reprograms-bone.html