Researchers find new biomarker for improved immunotherapy response in solid tumors
MD Anderson Research News October 16, 2025
- Study uncovers novel relationship between TET2-mutated white blood cells and antitumor immune responses
- TET2-mutated clonal hematopoiesis is associated with improved patient outcomes after immunotherapy treatment, highlighting its potential as a biomarker to select patients for treatment with immunotherapy
HOUSTON, OCTOBER 16, 2025 ¨D Researchers at Â鶹ӳ» MD Anderson Cancer Center used preclinical models to uncover a potential biomarker for improved immunotherapy responses, a finding that was validated in independent data sets of nearly 60,000 patients with solid tumors. The study was published today in .
This research describes a new mechanism for TET2 mutations to prime certain white blood cells, improving the presentation of antigens for immune recognition and leading to more activated T cells and an enhanced immunotherapy response. The study was led by , professor of Immunology and Genitourinary Medical Oncology and director of scientific programs for MD Anderson¡¯s James P. Allison Institute.
¡°We are encouraged by these results highlighting a new mechanism of action for TET2 mutations in improving responses to immunotherapy,¡± Sharma said. ¡°Exploring and understanding these complex relationships in solid tumor immunology allows us to develop more personalized treatments for our patients.¡±
What led the researchers to study TET2 mutations and immune responses?
Sometimes, a blood-producing stem cell can acquire a mutation that allows it to produce more clones of itself than other stem cells, leading to its overrepresentation in the blood. This phenomenon, called clonal hematopoiesis (CH), is found in over 10% of healthy adults and over 20% of patients with solid tumors. CH is associated with a much higher risk of developing blood diseases and with poor prognosis in patients with cancer.
The TET2 enzyme enhances stem cell self-renewal, and the TET2 gene is the second most mutated gene in patients with CH. Recently, TET2 was implicated to play a role in T cell responses, but TET2 mutations do not appear naturally in human T cells. This led Sharma to hypothesize that TET2 mutations, which have been identified in human myeloid cells, may affect the function of myeloid cells. The researchers then studied the impact of TET2-mutated CH on the immune microenvironment in models of pancreatic cancer and melanoma.
How did they find a biomarker for improved immunotherapy responses in solid tumors?
Shelley Herbrich, Ph.D., a postdoctoral fellow in Sharma¡¯s lab, developed in vivo models of TET2-mutated CH that accurately reflect the human condition in order to track the movement and function of these cells throughout solid tumors.
TET2-mutated CH was associated with improved response to combination immunotherapy in models of pancreatic cancer and melanoma, along with an increase in antigen presentation by pro-inflammatory white blood cells ¨C called macrophages or myeloid cells ¨C which resulted in more activated T cells.
Further analysis of a cohort of over 35,000 patients with non-small cell lung cancer (NSCLC) showed that patients with TET2-mutated CH had significantly improved overall survival with immunotherapy, which also was confirmed in a separate group of 25,064 patients with colorectal cancer.
These findings suggest that TET2-mutated CH is a potential biomarker for improved immunotherapy response, and that further investigation is warranted.
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This study was supported by the Parker Institute for Cancer Immunotherapy, the T.C. and Jeanette Hsu Foundation, and the Ergon Foundation Award. For a full list of collaborating authors, disclosures and funding sources, see the full paper in .
We are encouraged by these results highlighting a new mechanism of action for TET2 mutations in improving responses to immunotherapy. Exploring and understanding these complex relationships in solid tumor immunology allows us to develop more personalized treatments for our patients.