Prostate cancer immunotherapy yields superior long-term survival in TRAMP mice when administered at an early stage of carcinogenesis prior to the establishment of tumor-associated immunosuppression at later stages.
Prostate cancer immunotherapy clinical trials have been performed, but often in immunocompromised patients with limited clinical success. The study aim was to determine whether the stage of prostate cancer development at which immunization occurs affects vaccine efficacy, and if so which tumor-associated immunosuppressive mechanisms may be involved at later stages. Therapeutic vaccination of TRAMP mice with only precancerous PIN lesions confered superior protection to immunization after development of invasive carcinoma. The presence of Treg, upregulation of tumor indoleamine-2,3-dioxygenase and TGFbeta and an immunosuppressive intratumoral cytokine milieu were identified in more advanced prostate cancer. These results indicate that prostate cancer immunotherapy trials will be more successful if conducted in patients with less advanced disease.
Gray
Andrew
A
Department of Molecular Microbiology & Immunology, University of Southern California and Norris Comprehensive Cancer Center, Los Angeles, CA 90033, United States.
de la Luz Garcia-Hernandez
Maria
M
van West
Myrna
M
Kanodia
Shreya
S
Hubby
Bolyn
B
Kast
W Martin
WM
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D049109:Cell Proliferation; D007167:Immunotherapy / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use
D019496:Cancer Vaccines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016212:Transforming Growth Factor beta; D019444:Vaccines, DNA