Nat Immunol: As a worker, the immune cells will be "exhausted". The Nature publication teaches you how to "resurrect T cells" and eliminate cancer!

Tumor is a systemic disease, and its treatment process requires long-term planning, like a marathon, but due to the long confrontation in this tug-of-war, the T cells that fight tumors are unable to do what they want

Recently, scientists at the La Jolla Institute for Immunology (LJI) have found a breakthrough to solve this problem

Related research BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells was published in Nature Immunology magazine

As the most important immune cell in the human immune system, T cells play an indispensable role in resisting bacterial viruses and other foreign pathogens and killing cancer cells

On the contrary, if the costimulatory signal is lacking, the CD8+ T cells that infiltrate the tumor tissue for a long time will enter a state of "exhaustion or dysfunction", resulting in symptoms of immune incompetence and loss of anti-tumor ability

In fact, CD8+ T cell effects and depletion responses are both initiated by T cell receptor (TCR) signals, and nuclear factor of activated T cells (NFAT) is a type of transcription factor with multidirectional regulatory functions.

Therefore, in order to determine which transcription factor is more effective against cell failure, researchers transferred three NFAT-AP-1 active transcription factors "JUN, MAFF and BATF" into mouse models of melanoma and colorectal cancer, respectively.

BATF-transduced CAR T cells exhibit enhanced tumor rejection

Previous studies have shown that T cell depletion usually prevents T cells from producing a strong memory response to recurrent cancer.

BATF-transduced CAR T cells persist after tumor regression

In order to more effectively combat the T cell exhaustion program, the researchers found in further experiments that the combination of BATF and interferon regulatory factor 4 (IRF4) has a better effect.

BATF-IRF4 interaction is essential for anti-tumor response

Patrick G.

Original source:

Seo, H.