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.
Monsurrò
Vladia
V
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, Bldg. 10, R-1C711 National Institutes of Health, Bethesda, MD, USA.
Wang
Ena
E
Panelli
Monica C
MC
Nagorsen
Dirk
D
Jin
Ping
P
Katia
Zavaglia
Z
Smith
Kina
K
Ngalame
Yvonne
Y
Even
Jos
J
Marincola
Francesco M
FM
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