Excited to share that I have been named the next Chair of the Department of Immunology at Pitt! We have a fantastic department and immunology community here and I’m honored to have the opportunity to help it grow!.

RT @SciImmunology: Two new studies present insights into regulatory T cells located in tumors associated with head and neck squamous cell c….

This work is co-published with a complimentary study from @SmithImmunology and @dpardol1 groups, check out their exciting findings in detail at @SciImmunology!.

We are indented to members of the @VignaliLab for their help and advice, and colleagues in @UPMCHillmanCC and the Pitt Immunology Department. We are especially grateful to @TakisBenosLab, @BcellBruno, @RobertFerrisMD and all our collaborators for their contributions to this study.

These findings revealed a distinct transcriptional signature of an intratumoral Treg subpopulation that is associated with worse prognosis, identified distinct surface markers of TNFR+ Tregs and provides insights into immunotherapeutic targets for the treatment of solid tumors.

Our analyses highlighted the regulatory roles of BATF with several surface markers differentially expressed on HNSCC TIL Tregs.

The role of BATF in TNFR+ Tregs was further corroborated in human Tregs under the combination of continuous TCR activation and hypoxic condition that mirrored intratumoral TNFR+ Treg phenotypes.

Perturbation of BATF in human activated Tregs resulted in enhanced suppressive function as well as effects on multiple targets that associate with Treg stability, activation and suppression, including ICOS, neuropilin-1, LAG3 and IL35 subunit EBI3.

To validated our observations from single-cell analyses and to interrogate the phenotypic changes regulated by BATF, we employed CRISPR-Cas9 knockout technology to target ex vivo-cultured human primary activated Tregs.

We utilized computational systems approaches to reconstruct transcriptional networks at each Treg cell state. We found that the transcription factor BATF is a central component of the gene regulatory network that regulates the transcriptional signature of TNFR+ Tregs.

melanoma, lung cancer, breast cancer, colorectal cancer and ovarian cancer.

Our analyses revealed that TNFR+ Tregs are not only enriched in the HNSCC TME, but also in multiple solid TME and associated with worse prognosis across solid tumors. TNFR+ Tregs exhibit similar transcriptional phenotypes in two independent single-cell datasets including. .

We identified a subpopulation of activated Tregs expressing multiple tumor necrosis factor receptor member (TNFR+ Tregs) that are negatively associated with prognosis of patients with HNSCC.

To provide a detailed view on the heterogeneity of Tregs in the TME, we profiled single-cell transcriptomes of CD4+ T cells in tumors and peripheral blood from patients with HNSCC, in non-tumor tonsil tissues and in peripheral blood from healthy donors.

Regulatory T cells are phenotypically and functionally heterogenous in the TME, but what are the transcriptional networks of functionally suppressive Tregs in the TME?. Our latest work from the lab and first-author @Feng_Shan_ is out now at @SciImmunology!

See this link for more details and registration: 2/2.

I'm excited to be co-organizing the next FASEB Autoimmunity meeting with @montserrat!  We have an amazing speaker line up, and these meetings always include fantastic presentations, and outstanding participation and discussion (and are a lot of fun!). Please join us! 1/2

Tagging @OnkarSayali!.

Amazing collaborative effort and an honor (and fun) to work with @oesterreichs! And kudos to @OnkarSayali.

Excited to share our latest paper in @NatImmunol entitled "IFNγ-induction of TH1-like regulatory T cells controls antiviral responses". Kudos to first author @AngelaGocher! @UPMCHillmanCC