Advanced search
Start date
Betweenand

Role of lactic acid in the resistance to checkpoint inhibitors (anti-PD-1/PD-L1) used in cancer immunotherapy

Grant number: 17/25308-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: September 01, 2018
End date: September 02, 2023
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Fernando de Queiroz Cunha
Grantee:Carlos Wagner de Souza Wanderley
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
Associated scholarship(s):21/12898-8 - Targeting the Warburg effect to overcome primary resistance to anti-PD-1/PD-L1 blockage, BE.EP.PD

Abstract

The modulation of the immunological checkpoints with monoclonal antibodies anti-programmed cell death protein 1 (anti-PD-1), or anti-PD-1 ligand (anti-PD-L1) promotes the reactivation of antitumor immunity and produces unprecedented positive clinical responses in cancer treatment. However, 40-60% of patients presented a primary resistance to the anti-PD-1/PD-L1, which the mechanism is unknown. Currently, it is established in the literature that phenotypic and functional changes in immune cells are linked with metabolic adaptation. In line with this, it was demonstrated that lactic acid, a product of cellular glycolytic metabolism, inhibits CD8 T cell activation and favor the suppressor functions of the T regulatory cell through the increase of mitochondrial oxidative metabolism. Additionally, in the tumor microenvironment, the accumulation of lactic acid, a product from the glycolytic metabolism of neoplastic cells, was associated with the development of metastasis and less overall survival. These findings indicate that lactic acid is an immunosuppressive agent that participates of the tumor progression. However, the involvement of lactic acid in the resistance to anti-PD-1/PD-L1 treatment is still unknown. Therefore, we intend to investigate the role of lactic acid in the resistance to anti-PD-1/PD-L1 and to propose new immuno-pharmacological procedures that associated with checkpoint inhibitors could increase the efficacy of anti-cancer treatment.

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

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)
WANDERLEY, CARLOS WAGNER S.; MAGANIN, ALEXANDRE G. M.; ADJAFRE, BEATRIZ; MENDES, ATLANTE S.; SILVA, CONCEICAO ELIDIANNE ANIBAL; QUADROS, ANDREZA URBA; LUIZ, JOAO PAULO MESQUITA; SILVA, CAMILA MEIRELLES S.; SILVA, NICOLE R.; OLIVEIRA, FRANCISCO FABIO BEZERRA; et al. PD-1/PD-L1 Inhibition Enhances Chemotherapy-Induced Neuropathic Pain by Suppressing Neuroimmune Antinociceptive Signaling. CANCER IMMUNOLOGY RESEARCH, v. 10, n. 11, p. 10-pg., . (13/08216-2, 17/25308-9)
WANDERLEY, CARLOS WAGNER S.; CORREA, TATIANA STRAVA; SCARANTI, MARIANA; CUNHA, FERNANDO QUEIROZ; BARROSO-SOUSA, ROMUALDO. Targeting PARP1 to Enhance Anticancer Checkpoint Immunotherapy Response: Rationale and Clinical Implications. FRONTIERS IN IMMUNOLOGY, v. 13, p. 10-pg., . (17/25308-9)