IRF4 instructs effector Treg differentiation and immune suppression in human cancer
G Alvisi, J Brummelman, S Puccio, EMC Mazza… - The Journal of clinical …, 2020 - jci.org
The Journal of clinical investigation, 2020•jci.org
The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+
Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from
chemotherapy-naive individuals with non–small-cell lung cancer identified the transcription
factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with
superior suppressive activity. In contrast to the IRF4–counterparts, IRF4+ Tregs expressed a
vast array of suppressive molecules, and their presence correlated with multiple exhausted …
Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from
chemotherapy-naive individuals with non–small-cell lung cancer identified the transcription
factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with
superior suppressive activity. In contrast to the IRF4–counterparts, IRF4+ Tregs expressed a
vast array of suppressive molecules, and their presence correlated with multiple exhausted …
The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non–small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4– counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.
