Induction of the Transcriptional Repressor B Lymphocytes-Induced Maturation Protein-1 (Blimp-1) in Lung Cancer - European Medical Journal
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Induction of the Transcriptional Repressor B Lymphocytes-Induced Maturation Protein-1 (Blimp-1) in Lung Cancer

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EMJ Respiratory 8.1 2020 Feature Image
Authors:
Laura Neurath,1 Denis I. Trufa,2 Carol I. Geppert,3 Ralf J. Rieker,3 Horia Sirbu,2 *Susetta Finotto1
Disclosure:

The authors have declared no conflicts of interest.

Citation
EMJ Respir. ;8[1]:82-83. Abstract Review No. AR11.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

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BACKGROUND AND AIM

Lung cancer immunotherapy has improved the survival for patients with advanced non-small cell lung cancer(NSCLC). Immunotherapy could improve the prognosis for lung cancer by activation of tumour-infiltrating lymphocytes, which are silenced by the expression of T-cell receptor inhibitor molecules such as programmed cell death protein 1. Immunotherapy, such as antiprogrammed death-ligand 1 antibody therapy, results in the activation of tumour-infiltrating lymphocytes into cytotoxic CD4+ and CD8+ T cells in the tumour microenvironment and suppression of immune-repressing regulatory T cells (Treg).1 The authors previously demonstrated that the recognition and elimination of lung tumour cells by T lymphocytes requires the presence of T-box-expressed in T cells (T-bet), a transcriptional regulator that induces Th1 differentiation, which promotes cytolytic CD8+ T cells, natural killer, and natural killer T cells and inhibits Treg cells.Moreover, recent studies showed that IL-2 in the tumour microenvironment supports acquisition of cytotoxic activity by Th cells orchestrated by the transcriptional repressor B lymphocytes-induced maturation protein-1 (Blimp-1).3 As Blimp-1 also affects the homeostasis and function of CD4 and CD8+ T cells as well as Treg cells, the authors hypothesised that this transcription factor might play an important role in lung cancer.

METHODS

The authors have recently described their biobank obtained from a cohort of patients with NSCLC.Specifically, after lung resection, the authors immediately transported on ice the lung samples in cell culture medium to their department and froze samples immediately for further analysis. Next, proteins from these lung sections were extracted and the Blimp-1 protein expression was analysed by Western blot analysis using proteins isolated from the different region of the lung of a cohort of patients that underwent surgery because of NSCLC and subsequent histological classification as lung adenocarcinoma (ADC).

RESULTS

The authors found that patients with lung ADC had a significant induction of Blimp-1 protein expression in the tumoural region of ADC (solid tumour) as compared control lung region (tumour-free control area). The expression of T-bet in these patients was further analysed and it was found that T-bet, as opposed to Blimp-1, was mainly expressed in the control region of the lung of these patients and downregulated in the tumoral region. Next, the localisation of Blimp1 positive cells in the tumour microenvironment was analysed by immunostaining lung sections from the cohort of patients using anti-Blimp 1 antibodies followed by DAPI staining. Here, the accumulation of Blimp1-positive cells surrounding the tumour was observed, as compared to the control region.

CONCLUSION

In conclusion, these data suggest that Blimp-1 might represent an additional new marker to be considered in the absence of T-bet as regulator of antitumour immune responses in lung cancer.

References
Waldman AD et al. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;1-18. Reppert S et al. A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer. Nat Commun. 2011;2:600. Śledzińska A et al. Regulatory T cells restrain interleukin-2- and blimp-1-dependent acquisition of cytotoxic function by CD4 + T cells. Immunity. 2020;52(1):151-66.e6. Nutt SL et al. BLIMP1 guides the fate of effector B and T cells. Nat Rev Immunol. 2007;7(12):923-39. Martins G, Calame K. Regulation and functions of Blimp-1 in T and B lymphocytes. Annu Rev Immunol. 2008;26:133-69. Heim L et al. NFATc1 promotes antitumoral effector functions and memory CD8 + T-cell differ-entiation during non-small cell lung cancer development. Cancer Res. 2018;78(13):3619-33.