The transcription factor Blimp-1 is suppressed by SLAMF1 and drives Treg cell-mediated immune evasion in non-small
Susetta Finotto1,2,3,4, Denis I Trufa5,6,7, Sonja Trump8
1Department of Molecular Pneumology, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, 91054, Erlangen, Germany. susetta.finotto@uk-erlangen.de.
Background:
Immune checkpoint inhibitors targeting the interaction between PD1 and PDL1 are effective for immunotherapy in non-small cell lung cancer (NSCLC). However, only subgroups of patients respond to therapy, suggesting the existence of resistance mechanisms.
Methods:
In this study, we analyzed post-surgery lung tissues and peripheral blood cells from patients with Non Small Cell Lung Cancer (NSCLC) and control subjects by using western blot, immunohistochemistry, ELISA, multiplex cytokine, and qPCR analysis.
Results:
Here, we found progressively increased Blimp1 expression in the tumoral region of NSCLC patients, where Slamf1 significantly decreased, and it inversely correlated with Blimp1. In PBMCs, Blimp1 was expressed in CD8+ T cells but predominantly in immunosuppressive Foxp3+ Treg cells or after targeting of the T cell activator Slamf1. Anti-CD3/CD28 induced IL-6 and IL-10, an immunosuppressive gene induced by Blimp1, in the supernatants of PBMCs from patients with NSCLC. Targeting PD1 in PBMCs reduced Blimp1.
Conclusions:
Here, we identify a key role of the transcription factor Blimp1 for immune evasion in NSCLC. Thus, targeting Blimp1 emerges as a novel concept to improve current lung cancer immunotherapies and to suppress immune evasion in lung cancer.
Insights
Blimp1, a transcription factor, drives immune evasion in non-small cell lung cancer (NSCLC). Targeting Blimp1 offers a new strategy to enhance immunotherapy effectiveness for lung cancer patients.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Immune checkpoint inhibitors (ICIs) targeting PD1/PDL1 interaction show efficacy in non-small cell lung cancer (NSCLC) immunotherapy.
- Patient response to ICIs varies, indicating underlying resistance mechanisms.
- Understanding these resistance mechanisms is crucial for improving NSCLC treatment outcomes.
Purpose of the Study:
- To investigate the role of transcription factor Blimp1 in immune evasion within NSCLC.
- To explore Blimp1's correlation with other immune markers like Slamf1.
- To identify novel therapeutic targets for overcoming resistance in NSCLC immunotherapy.
Main Methods:
- Analysis of post-surgery lung tissues and peripheral blood cells from NSCLC patients and controls.
- Utilized techniques including western blot, immunohistochemistry, ELISA, multiplex cytokine analysis, and qPCR.
- Investigated Blimp1 expression and its correlation with Slamf1 in different immune cell populations.
Main Results:
- Blimp1 expression was progressively increased in the tumoral region of NSCLC patients, inversely correlating with decreased Slamf1.
- In peripheral blood mononuclear cells (PBMCs), Blimp1 was found in CD8+ T cells and predominantly in immunosuppressive Foxp3+ Treg cells.
- Anti-PD1 treatment in PBMCs reduced Blimp1 expression, and Blimp1 induction correlated with immunosuppressive cytokines IL-6 and IL-10.
Conclusions:
- The transcription factor Blimp1 plays a critical role in immune evasion in NSCLC.
- Targeting Blimp1 presents a novel therapeutic strategy to enhance current lung cancer immunotherapies.
- Inhibiting Blimp1 may help overcome immune evasion and improve treatment responses in NSCLC.
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