The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma

ABSTRACT

Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4⁺ T cells, expressing both, Tbet and Foxp3. Although Tbet⁺Foxp3⁺ T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet⁺Foxp3⁺CD4⁺ T cells, mediated by the immunosuppressive cytokine TGFβ in the lungs of tumour bearing mice. This is in line with previous studies, demonstrating the important role of TGFβ for the immunopathogenesis of cancer. By gathering results both in murine model and in human disease, we demonstrate that, the conversion of IFNγ producing anti-tumoral T-bet+Th1 CD4+ T cells into immunosuppressive Tbet and Foxp3-PD1 co-expressing regulatory cells could represent an additional important mechanism of TGFβ-mediated blockade of anti-tumour immunity.

KEYWORDS:

• Tbet
• Foxp3
• PD1
• NSCLC
• Immunotherapy

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors thank the whole team of the Molecular Pneumology department at the University of Erlangen for their technical support. We also thank Kinga Soó Becker from the University of Mainz, providing us with the results on the survival of hCD2-ΔkTβRII as compared to WT mice upon tumor induction. This work was supported by an ELAN16-05-24-1-Andreev Grant awarded to Katerina Kachler, by the IZKF grant A59 and by the grant B12 in the SFB643 both awarded to Susetta Finotto and by the Molecular Pneumology department at the University FAU Erlangen-Nürnberg.

Author contributions

S.F. supervised the research and helped with data analysis as well as with writing and the revision of the manuscript. K.K designed and performed the experiments presented in this study, analysed the data in the paper and wrote the manuscript. D.I.T. contributed to cell isolation from lung tissue obtained after surgery from patients. H.S. and D.I.T. contributed to selection of patients, performed surgery and collected the clinical data. The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to S.F. ([email protected]).

Additional information

Funding

This work was supported by an ELAN 16-05-24-1-Andreev Grant awarded to Katerina Kachler, by the IZKF grant A59 and by the grant B12/SFB643 both awarded to Susetta Finotto and by the Molecular Pneumology department at the University FAU Erlangen-Nürnberg.