Active-specific immunization against melanoma: is the problem at the receiving end?
The recent progress in tumor immunology is a striking example of the successful application of modern biotechnology to understand the complex phenomenon of immune-mediated cancer rejection. Tumor antigens were identified and successfully utilized in active immunization trials to induce tumor antigen-specific T cells. This achievement has left, however, clinicians and researchers perplexed by the paradoxical observation that immunization-induced T cells can recognize tumor cells in standard assays but cannot induce tumor regression. A closer look at T cell physiology and tumor biology suggests that this observation is not so surprising. Here, we argue that successful immunization is one of several steps required for tumor clearance while more needs to be understood about how T cells localize and are effective within a tumor microenvironment impervious to the execution of their effector function.
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, Bldg. 10, R-1C711 National Institutes of Health, Bethesda, MD, USA.
Vladia
V
Monsurrò
Ena
E
Wang
Monica C
MC
Panelli
Dirk
D
Nagorsen
Ping
P
Jin
Zavaglia
Z
Katia
Kina
K
Smith
Yvonne
Y
Ngalame
Jos
J
Even
Francesco M
FM
Marincola
D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007114:Immunization; D016233:Immunotherapy, Active; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D007376:Interleukin-2