Targeting Blimp-1 in T cells results in activation of T-bet-mediated control of immunosuppression in lung cancer

Finotto S, Chiriac MT, Krammer S, Yang Z, Neurath L, Geppert CI, Nendel E, Trump S, Geiger A, Wirtz S, Zundler S, Neurath M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cancer Immunology, Immunotherapy Springer Verlag (Germany)

Book Volume: 75

Article Number: 144

Journal Issue: 5

DOI: 10.1007/s00262-026-04381-4

Abstract

Background: Lung cancer is the leading cause of cancer-related death in the world. Blimp-1 is a transcriptional repressor that, by interacting with other transcription factors in lymphocytes, regulates their cellular fate. Objective: In this study, we focused on the role of Blimp-1 in T cells in lung cancer. Methods: Here, we analyzed, in a murine model of NSCLC, the role of Blimp-1 in T cells after targeting Blimp-1 in T cells expressing lymphocyte-specific-protein tyrosine kinase (Lck), a kinase crucial for T-cell receptor signaling. Results: We found that mice lacking Blimp1 expression in T cells have reduced lung tumor load, suppressed lung Foxp3+Treg cells in the lung and draining lymph nodes, and induced T-bet+CD4+T effector cells producing IFN-gamma and interleukin-2. Furthermore, RNA sequencing of spleen CD4+T cells showed an induction of Th1 markers, including TNF, IL-2 and interferon type I-related genes, but also PD1. RNA sequencing of spleen CD8+T cells showed induced Tc1 markers, including IL12rb1, CD44, granzyme M and eomesodermin, in the absence of Blimp1. Finally, in the lung of mice with Blimp1 deficiency in T cells, we found an upregulation of CD8+T cells with increased release of cytotoxic mediators able to induce lung tumor cell death. Conclusions: These data indicate that the tumor microenvironment induces Blimp-1 in immunosuppressive Treg and T effector cells, thereby limiting the therapeutic efficacy of anti-tumor immune responses. Targeting of Blimp-1 in T cells emerges as a novel concept to suppress immune evasion in lung cancer by regulating CD4+, CD8+and Treg function in the lung.

Authors with CRIS profile

Mircea-Teodor Chiriac Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Susanne Krammer Department of Molecular Pneumology Zuqin Yang Department of Molecular Pneumology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Sebastian Zundler Professur für Immunzellmigration (Else Kröner Clinician Scientist Professur) Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1)

Involved external institutions

Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE)

How to cite

APA:

Finotto, S., Chiriac, M.-T., Krammer, S., Yang, Z., Neurath, L., Geppert, C.I.,... Neurath, M. (2026). Targeting Blimp-1 in T cells results in activation of T-bet-mediated control of immunosuppression in lung cancer. Cancer Immunology, Immunotherapy, 75(5). https://doi.org/10.1007/s00262-026-04381-4

MLA:

Finotto, Susetta, et al. "Targeting Blimp-1 in T cells results in activation of T-bet-mediated control of immunosuppression in lung cancer." Cancer Immunology, Immunotherapy 75.5 (2026).

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