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"Fighting a tumor is a marathon, not a sprint. For cancer-fighting T cells, the race is sometimes just too long, and the T cells quit fighting. Researchers even have a name for this phenomenon: T cell exhaustion.
In a new Nature Immunology study, researchers at La Jolla Institute for Immunology (LJI) report that T cells can be engineered to clear tumors without succumbing to T cell exhaustion. ...
The new study addresses this problem by giving T cells the ability to fight exhaustion itself.
To accomplish this, the researchers screened T cells to uncover which transcription factors could boost a T cell’s “effector” program, an important step in readying T cells to kill cancer cells.
This screening process led the researchers to BATF, a transcription factor that they found cooperates with another transcription factor called IRF4 to counter the T cell exhaustion program.
In mouse melanoma and colorectal carcinoma tumor models, altering CAR T cells to also overexpress BATF led to tumor clearance without prompting T cell exhaustion. The CAR T therapy worked against solid tumors. ...""Here, we show that basic leucine zipper ATF-like transcription factor (BATF) and interferon regulatory factor 4 (IRF4) cooperate to counter T cell exhaustion in mouse tumor models. Overexpression of BATF in CD8+ T cells expressing a chimeric antigen receptor (CAR) promoted the survival and expansion of tumor-infiltrating CAR T cells, increased the production of effector cytokines, decreased the expression of inhibitory receptors and the exhaustion-associated transcription factor TOX and supported the generation of long-lived memory T cells that controlled tumor recurrence."
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