Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital

• Grant number: 19/07111-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2021
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Lidia Maria Rebolho Batista Arantes
• Grantee: Lidia Maria Rebolho Batista Arantes
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated researchers: Ana Carolina de Carvalho Peters ; André Lopes Carvalho ; Matias Eliseo Melendez ; Pedro Rafael Martins De Marchi ; Robert Louis Ferris ; Rui Manuel Vieira Reis ; Vinicius de Lima Vazquez
• Associated scholarship(s): 24/05090-2 - Evaluation of PD-1, TIM-3 and LAG-3 checkpoint inhibitors in 3D models of irradiated head and neck tumor cell cultures, BP.MS; 24/08589-8 - Immune checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, BP.TT; 24/03967-4 - Analysis of the Predictive Potential of Histopathological Markers in the Response to Immunotherapy in Patients with Melanoma, BP.IC; + associated scholarships 22/16387-0 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, BP.TT; 22/14338-2 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, BP.TT; 22/05134-4 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, BP.TT; 21/10818-7 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, BP.TT; 21/08352-0 - Immune-checkpoint inhibitors: biomarkers to predict response in non-small cell Lung Cancer patients, BP.DD; 21/04100-6 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, BP.JP - associated scholarships

Abstract

Cancer immunotherapy is based on the premise that tumors can be recognized and can be attacked by an activated immune system. However, tumor cells develop mechanisms to thwart immune recognition and response. The immune checkpoints modulate the homeostasis of co-stimulatory and co-inhibitory signals, which are critical to maintaining immune tolerance besides modulating the physiological immune responses. However, despite the high response rate to immunotherapy, some patients are refractory to therapy or acquire resistance. Therefore, the characterization of the immune tumor microenvironment that drives or prevents effective responses to therapy is fundamental for understanding and expanding the use of immunotherapy. To investigate immunological markers that may distinguish responders from non-responders to therapy with immunological checkpoint inhibitors in patients with advanced melanoma and Non-small-cell lung carcinoma (NSCLC). One hundred patients who underwent anti-PD-1/PD-L1 or anti-CTLA-4 immunotherapy will be selected. The immunophenotypic profile of the immune checkpoint inhibitors will be evaluated on peripheral blood T lymphocytes and tumor infiltrating lymphocytes (TIL) by flow cytometry. The expression profile of relevant genes to cancer immune response will be analyzed in tumor samples (paraffin and CD45 negative cells), by PanCancer IO 360 Gene Expression Panel, using the nCounter NanoString platform. The expression profile of lymphocytes (from blood and tumor), paraffin material (containing tumor + TIL) and negative CD45 cells will be correlated with demographic, clinical, histopathological data and mainly with the therapeutic response and patient survival. Essential as a platform for this and later studies will be the enhancement and implementation of in vitro T lymphocyte exhaustion model, which will be performed by sequential stimulation with CD3/CD28 dynabeads. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TOSTES, KATIANE; SIQUEIRA, ALEXIA POLO; REIS, RUI MANUEL; LEAL, LETICIA FERRO; ARANTES, LIDIA MARIA REBOLHO BATISTA. Biomarkers for Immune Checkpoint Inhibitor Response in NSCLC: Current Developments and Applicability. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 15, p. 18-pg., 2023-08-01. (21/08352-0, 21/04100-6, 19/07111-9)

TEIXEIRA, RENAN J.; DE SOUZA, VINICIUS G.; SORROCHE, BRUNA P.; PAES, VICTOR G.; ZAMBUZI-ROBERTO, FABIANA A.; PEREIRA, CAIO A. D.; VAZQUEZ, VINICIUS L.; ARANTES, LIDIA M. R. B.. Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy. Melanoma Research, v. 34, n. 3, p. 7-pg., 2024-06-01. (19/07111-9, 21/10922-9, 19/03570-9)

SORROCHE, BRUNA PEREIRA; TEIXEIRA, RENAN DE JESUS; PEREIRA, CAIO AUGUSTO DANTAS; SANTANA, IARA VIANA VIDIGAL; VUJANOVIC, LAZAR; VAZQUEZ, VINICIUS DE LIMA; ARANTES, LIDIA MARIA REBOLHO BATISTA. PD-L1 Tumor Expression as a Predictive Biomarker of Immune Checkpoint Inhibitors' Response and Survival in Advanced Melanoma Patients in Brazil. DIAGNOSTICS, v. 13, n. 6, p. 11-pg., 2023-03-01. (19/03570-9, 21/04100-6, 19/07111-9, 21/10922-9)