The Role of Somatic Mutations on the Immune Response of the Tumor Microenvironment in Prostate Cancer

Author(s)

Melo, Camila Morais ^[1] ; Vidotto, Thiago ^[1] ; Chaves, Luiz Paulo ^[1] ; Lautert-Dutra, William ^[1] ; Reis, Rodolfo Borges dos ^[2] ; Squire, Jeremy Andrew ^{[3, 1]}

Affiliation

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Genet, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Div Urol, Dept Surg & Anat, BR-14048900 Ribeirao Preto, SP - Brazil

^[3] Queens Univ, Dept Pathol & Mol Med, Kingston, ON K7L 3N6 - Canada

• Document type: Review article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 17 SEP 2021.
• Web of Science Citations: 0

Abstract

Immunotherapy has improved patient survival in many types of cancer, but for prostate cancer, initial results with immunotherapy have been disappointing. Prostate cancer is considered an immunologically excluded or cold tumor, unable to generate an effective T-cell response against cancer cells. However, a small but significant percentage of patients do respond to immunotherapy, suggesting that some specific molecular subtypes of this tumor may have a better response to checkpoint inhibitors. Recent findings suggest that, in addition to their function as cancer genes, somatic mutations of PTEN, TP53, RB1, CDK12, and DNA repair, or specific activation of regulatory pathways, such as ETS or MYC, may also facilitate immune evasion of the host response against cancer. This review presents an update of recent discoveries about the role that the common somatic mutations can play in changing the tumor microenvironment and immune response against prostate cancer. We describe how detailed molecular genetic analyses of the tumor microenvironment of prostate cancer using mouse models and human tumors are providing new insights into the cell types and pathways mediating immune responses. These analyses are helping researchers to design drug combinations that are more likely to target the molecular and immunological pathways that underlie treatment failure. (AU)

• FAPESP's process: 19/22912-8 - Characterization of the genetic mechanisms leading to immune evasion in the tumor microenvironment of Prostate Cancer
• Grantee: Jeremy Andrew Squire
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/12816-9 - Does ZEB1 cooperate with PTEN loss and TMPRSS2-ERG fusion in prostate cancer immune evasion?
• Grantee: Luiz Paulo Chaves de Souza
• Support Opportunities: Scholarships in Brazil - Master