A prospective study to elucidate systemic and tumor microenvironment immunoregulatory networks related to anti-PD1 treatment failure in stage IV NSCLC and melanoma patients

• Grant number: 18/06409-1
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): July 01, 2018
• Effective date (End): July 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal researcher: Kenneth John Gollob
• Grantee: Amanda Braga de Figueiredo
• Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

The overall rate in patients treated with anti-PD1 therapy is up to 45% as first line therapy in patients with non-small cell lung cancer (NSCLC). In patients with malignant melanoma, the efficacy is around 30%. The elucidation of the factors responsible for treatment failure is fundamental for the development of new therapeutic approaches. Two factors are essential for influencing the patient's response to treatment: the nature of a patient's immunoregulatory environment, including antigen presenting cells (APCs) and T lymphocytes subpopulations, and the genomic landscape of the tumor itself, as indicated by mutational load and generation of neoantigens. We hypothesize that the balance between subpopulations of APCs and T lymphocytes can predict the response of patients with NSCLC or melanoma to immunotherapy, which can in turn be influenced by the tumor genomic landscape. He proposed to perform a non-interventional, prospective cohort study evaluating the immune status by enrolling 40 metastatic melanoma and 40 NSCLC stage IV patients treated with anti-PD1 (as first-line therapy) followed over 24 months, during which time individuals will segregate into responders and non-responders to treatment. We will evaluate the cellular immune profile in the tumor tissue and in the peripheral blood, the tumor infiltrating leukocytes in the tissue biopsy and the soluble immune profile, besides the tumor genomic landscape. The identification of markers of responsiveness, as well as clarifying the mechanisms responsible for the therapeutic failure, will indicate new approaches towards development of adjuvant therapies to anti-PD1 treatment.