Immunologic Monitoring of Cellular Immune Responses in Cancer Vaccine Therapy

Copyright © 2011 Theresa L. Whiteside et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Immunotherapy for cancer is based on the concept of inducing the generation and expansion of immune cells that can attack and eliminate cancer. Immunotherapy with therapeutic cancer vaccines aims specifically at inducing tumor antigen-specific T cells. The immune system is a complex, multifaceted cellular network that is not fully understood. Monitoring cellular immune responses is essential for rational cancer vaccine development. The primary objectives of immune monitoring after vaccination are to document the induction of vaccine-specific and tumor-specific immune responses and to correlate the presence and magnitude of vaccine-induced immune responses to clinical outcomes. Immune monitoring could also be used to (a) define the ability of a given vaccine to generate antigen cascade responses (i.e., epitope spreading); (b) compare the effects of vaccines of different potencies; (c) evaluate the ability of a given cytokine, drug, adjuvant, and so forth. to enhance or hinder vaccine-induced immune responses; (d) define appropriate patient populations for vaccine studies; (e) study the presence and activity of inhibitory/ suppressor cell populations. Despite advances in the development of immune monitoring assays during the past decade, it has been difficult to establish significant correlations between vaccine-induced immune responses and clinical outcomes. This lack of correlation could reflect the methodological limitations of immunologic assays or the postvaccination absence of antitumor responses sufficiently robust to induce disease-free or overall survival. A wide portfolio of monitoring assays is currently available. However, these assays fail to define surrogate markers that could be used as predictors of clinical response and thus serve to advance vaccine development. The immune monitoring assays currently used in cancer immunotherapy trials (such as enzyme-linked immunospot assays, tetramer-based assays, intracellular cytokine flow cytometry, antibody tests, proliferation assays, reverse transcription polymerase chain reaction, and serum cytokine and chemokine profiles) have limited usefulness as surrogate markers of clinical efficacy. There is general consensus that further studies are needed to account for the difficulties in establishing the correlation between different aspects of T-cell function and clinical efficacy. Vaccine-induced immune responses against cancer depend on a balance between immune responses of various subsets of effector and suppressor T cells. Because tumor antigens are mostly self-antigens, this balance is shifted toward tolerance in cancer patients, so …