Thymic Polypeptide Fraction Biomodulina T Decreases Exhausted and Terminally Differentiated EMRA T Cells in Advanced Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

Gisela María Suárez,Tania Crombet,Manuel Díaz,Agustin Lage,Ana Laura Añé-Kourí,Zaima Mazorra,Raúl Ramos,Patricia Lorenzo-Luaces,Yadira Peña,Susana Portela,María De Los A Molina,Mauricio Catalá,Karla Pereira,Amnely González,Jenysbel De La C Hernández,Mary Carmen Reyes,Nuris Ledón,Danay Saavedra

doi:10.3389/fonc.2022.823287

Abstract

Lung cancer is the second cause of cancer related deaths worldwide. Chemotherapy and immunotherapy represent the current standard of care for advanced NSCLC. Platinum-based chemotherapy expands late-differentiated T cell populations. Therefore, immune restoration after chemotherapy to adjuvate the immunotherapeutic potential could be crucial. The aim of this study was to evaluate the effect of Biomodulina T (BT), a thymic polypeptide fraction, on peripheral lymphocytes subpopulations in the context of cancer disease. Additionally, whether these effects might induce a better response to CIMAvax-EGF, an epidermal growth factor (EGF) depleting immunotherapy. Eighteen advanced NSCLC patients were evaluated after being treated with platinum-based chemotherapy. We found that the frequency of terminally differentiated effector T cells re-expressing CD45RA (EMRA) CD4+ (p=0.0031) and CD8+ (p=0.0372) T cells decreased with the administration of BT, whereas CD4+ naive T cells increase in more than 70% of the patients. Remarkably, CD4+ and CD8+ T lymphocytes expressing programmed cell death receptor-1 (PD1) significantly decreased after BT administration (p=0.0005 and p<0.0001, respectively). We also found an enhancement of the anti-EGF antibody response with a large percentage of patients treated with CIMAvax-EGF reaching the good antibody response condition after four vaccine doses. Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.

Highlights

IntroductionLung cancer is the leading cause of cancer death in 2020, with an estimated 2.2 million new cases and 1.8 million deaths [1]
Cancer’s rising prominence is a major health problem around the world
The analysis showed a significant decrease in the percentage of EMRA CD4+ T cells at the end of treatment with BT (p=0.0031; Wilcoxon test; Figures 2A, B)

Summary

Introduction

Lung cancer is the leading cause of cancer death in 2020, with an estimated 2.2 million new cases and 1.8 million deaths [1]. The most common form of the disease is NSCLC and more than 60% of patients have advanced illness at diagnosis [2]. Cancer immunotherapy has been shown to increase survival of patients with advanced cancer [3]. Several immunomodulatory drugs, including antiPD-1 antibodies such as nivolumab and pembrolizumab have shown an improvement in the survival of patients with advanced NSCLC [4,5,6]. The molecular heterogeneity of NSCLC makes it more difficult for diagnosis and for the management and therapeutic response in cancer patients [7]

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