Tumors accumulate expanded GATA3-dependent tissue Tregs

Kunesch, K.; Bharadwaj, S.; Tearle, J. L. E.; Kopplin, L.; Desveaux, I.; Laouina, A.; Ticconi, F.; Wild, A. B.; Taketo, M. M.; Stemmler, M. P.; Cramer, T.; Hansen, G.; Neumann, U.; James, K. R.; Pabst, O.; Izcue, A.

doi:10.64898/2026.03.13.707380

bioRxiv · 10.64898/2026.03.13.707380

Tumors accumulate expanded GATA3-dependent tissue Tregs

Kunesch, K.·Bharadwaj, S.·Tearle, J. L. E.·Kopplin, L.·Desveaux, I.·Laouina, A.·Ticconi, F.·Wild, A. B.·Taketo, M. M.·Stemmler, M. P.·Cramer, T.·Hansen, G.·Neumann, U.·James, K. R.·Pabst, O.·Izcue, A.

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Abstract

Targeting Tregs is a potential strategy to improve cancer therapies. However, which Tregs accumulate in response to tumoral processes, and how tumors affect their phenotype, is poorly understood. Here we show that tumor Tregs are equivalent to effector tissue Tregs in steady state organs. We used a mouse model of intestinal neoplasia to demonstrate that one early event in carcinogenesis is sufficient to induce local accumulation of Tregs resembling human tumor Tregs. Treg accumulation was driven by TCR-dependent oligoclonal expansion of tissue Tregs with an effector Treg phenotype. Treg expansion was independent of CCR8, IL33R and CD137, which were previously linked to tumor Treg. In contrast, GATA3 was required for effector tissue Tregs and for their expansion in response to neoplasia. Our findings identify GATA3-dependent clonal expansion of effector tissue Tregs as a key event in promoting tumor growth. HighlightsO_LIAn early tumorigenic event alone drives accumulation of effector tissue Tregs C_LIO_LITregs in tumors are phenotypically akin to effector tissue Tregs C_LIO_LIThe accumulation of Tregs is driven by TCR-dependent oligoclonal expansion C_LIO_LIGATA3 controls tumor-promoting effector tissue Tregs C_LI

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Kunesch, K., Bharadwaj, S., Tearle, J. L. E., Kopplin, L., Desveaux, I., Laouina, A., Ticconi, F., Wild, A. B., Taketo, M. M., Stemmler, M. P., Cramer, T., Hansen, G., Neumann, U., James, K. R., Pabst, O., Izcue, A.. 2026-03-15. Tumors accumulate expanded GATA3-dependent tissue Tregs. https://doi.org/10.64898/2026.03.13.707380

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