Several activities including meetings and working groups highlighting the importance of the immune infiltrate in cancer prognosis and response to therapy as well as analytically validated assays for clinical application have been held since 2007. These meetings were co-sponsored by CDP, Office of International Affairs, and Office of Rare Disease Research at NCI and the Society for Immunotherapy of Cancer (SITC), formerly international Society for Biological Therapy of cancer (iSBTc). Meetings entitled “Profiling of Immune Response to Guide Cancer Diagnosis, Prognosis, and Prediction of Therapy” and the “U.S.-Japan Workshop on Immunological Biomarkers in Oncology" pointed out a link between prognosis and/or response to therapy and immune infiltrates in tumors. Immunological criteria including inflammatory cells, immune modulators, and variations in the host genetic background have been shown not only to be independent indicators of prognosis but can also predict response to treatment. However, evaluation of immune infiltrates is complex and can vary among different cancer types. Thus, rigorous approaches for comprehensive analysis and standardization of lymphocytic reactions including CD8+ T lymphocytes, myeloid cells, regulatory T-cell responses, cytokines, and chemokines and functional genetic variations in immune regulatory genes need to be developed. As these variables become useful, clinically proven metrics, they could improve current measures of staging criteria for prognosis and identifying subgroups of a high-risk population of tumors, thus influencing current strategies for effective cancer treatments. These meetings also addressed study design, statistical approaches, and tissue resource availability.
Tahara H, et al. Emerging concepts in biomarker discovery; the US-Japan Workshop on Immunological Markers in Oncology. J Transl Med 2009:7;45. http://www.ncbi.nlm.nih.gov/pubmed/19534815
Ambs S, Marincola FM, Thurin M. Profiling of immune response to guide cancer diagnosis prognosis and prediction to therapy--meeting report. Cancer Res 2008:68;4031-33. http://www.ncbi.nlm.nih.gov/pubmed/18519659
The meeting reporting activities of the iSBTc/FDA/NCI Task Force on Immunotherapy Biomarkers (iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer) mainly addressed issues relevant to correlation between immunological end-points and clinical outcomes of immunotherapy including anti-cancer vaccine therapy. Immunotherapy of cancer is becoming a part of standard management of cancer patients. The FDA has recently approved the first therapeutic cancer vaccine (sipuleucel-T) and T cell stimulatory drug (ipilimumab). However, there is a need for biomarkers and standardized immunological assays to identify patients who will benefit from a particular form of therapy as well as monitoring effectiveness of various biological therapies. In addition, assays to assess the potency of biological therapeutics (vaccines, adaptive T-cell therapeutics) are required. The task force addressed challenges to immune-based therapies and provided recommendations as to how improvements in these areas could facilitate the translation of these assays into the clinic.
Butterfield LH, et al. Recommendations from the iSBTc/FDA/NCI Workshop on Immunotherapy Biomarkers. Clin Cancer Res 2011:17;3064-76. http://www.ncbi.nlm.nih.gov/pubmed/21558394
Butterfield LH, et al.A systematic approach to biomarker discovery; preamble to the iSBTc-FDA taskforce on immunotherapy biomarkers. J Transl Med 2008:6;81. http://www.ncbi.nlm.nih.gov/pubmed/19105846