Impact of CDK12 mutation on immune response in prostate cancer

• Grant number: 21/12271-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2022
• End date: December 31, 2022
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Jeremy Andrew Squire
• Grantee: William Lautert Dutra
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Background: Treatment of advanced PCa remains a therapeutic challenge. Moreover, new immunotherapies like immune-checkpoint blockade (ICB) have shown significant benefits in only a minority of patients. CDK12 defect-PCa is a recently discovered molecular subtype of this tumor with a high neoantigen load and increased immune cell infiltrate. CDK12 defective PCa has variable results with recent immunotherapy clinical trials. Thus, we hypothesize CDK12 loss leads to distinct gene expression changes that increase the immune evasion capacity of PCa. Methods: We will identify somatic mutations that affect CDK12 alleles in both primary and metastatic prostate cancer. We will correlate the frequency of somatic mutations with the changes in the transcriptional profile and TME of CDK12-wt (CDK12+/+) and CDK12-mut (CDK12+/-; -/-) using public domain data. Implications: We suggest that an improved understanding of the molecular basis of the CDK12-dependent immune evasion phenotype will provide helpful information about the causes of immunotherapy failure in PCa.

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)

LAUTERT-DUTRA, WILLIAM; DOS REIS, RODOLFO BORGES; SQUIRE, JEREMY A.. Precision medicine for prostate cancer-improved outcome prediction for low-intermediate risk disease using a six-gene copy number alteration classifier. BRITISH JOURNAL OF CANCER, v. 128, n. 12, p. 2-pg., 2023-04-29. (19/22912-8, 21/12271-5)

VIDOTTO, T.; MELO, C. M.; LAUTERT-DUTRA, W.; CHAVES, L. P.; REIS, R. B.; SQUIRE, J. A.. Pan-cancer genomic analysis shows hemizygous PTEN loss tumors are associated with immune evasion and poor outcome. SCIENTIFIC REPORTS, v. 13, n. 1, p. 13-pg., 2023-03-28. (20/12816-9, 19/22912-8, 21/12271-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DUTRA, William Lautert. Impact of CDK12 mutation on immune response in prostate cancer. 2023. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.