Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer

Abstract

Knowledge of the basic mechanisms of the immune system as it relates to cancer has been increasing rapidly. These developments have accelerated the translation of these advancements into medical breakthroughs for many cancer patients. The immune system is designed to discriminate between self and non-self, and through genetic recombination there is virtually no limit to the number of antigens it can recognize. Thus, mutational events, translocations, and other genetic abnormalities within cancer cells may be distinguished as “altered-self” and these differences may play an important role in preventing the development or progression of cancer. However, tumors may utilize a variety of mechanisms to evade the immune system as well. Cancer biologists are aiming to both better understand the relationship between tumors and the normal immune system, and to look for ways to alter the playing field for cancer immunotherapy. Summarized in this review are discussions from the 2013 SITC Primer, which focused on reviewing current knowledge and future directions of research related to tumor immunology and cancer immunotherapy, including sessions on innate immunity, adaptive immunity, therapeutic approaches (dendritic cells, adoptive T cell therapy, anti-tumor antibodies, cancer vaccines, and immune checkpoint blockade), challenges to driving an anti-tumor immune response, monitoring immune responses, and the future of immunotherapy clinical trial design.

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

“…IFNs, tumor necrosis factor-a (TNF-a), IL-1, IL-4, IL-6, IL-10, IL-12, and IL-23), which control concomitant T-cell responses. 11 Three interactive signals are generally required for functional DE activation and subsequent development of innate and adaptive immunity against cancers, including adequate presentation of MHC-peptide complexes to DCs for T cell priming, upregulation of co-stimulatory molecules such as CD40, CD80, and CD86, and production of activating cytokines by T cells. 12 Classically activated macrophages (M1s) Tumor-associated macrophages (Ms) constitute one of the major cellular compartments of the tumor microenvironment, exerting a significant functional influence over tumor development.…”

Adoptive immunotherapy via CD4+ versus CD8+ T cells

“…These memory antigen-specific T cells play an important role in preventing tumor relapse. Compared to naïve T cells, when the memory T cells encounter tumor antigen at a later time, they demonstrate enhanced recognition, robust antitumor responses and long-lasting memory (Raval et al, 2014). Therefore, induction of a memory response is a major goal of cancer immunotherapy strategies.…”

“…CD8+ T cells). While CD8+ T cells have been the main focus of ACT trials, for their robust tumor cell killing ability (Restifo et al, 2012;Yee et al, 2002), it is also important to evaluate Th cells as a strategic alternative since they play a pivotal role in augmenting CTL responsiveness. Next-generation cancer vaccines, including Th epitopes, have been used to prime Th cells in vivo prior to extraction for ex vivo expansion.…”

“…Early tumors are eliminated by the immune system ("elimination" phase) and as cancers evolve, they continue to be held in check by the immune system ("equilibrium" phase) until their advanced growth becomes too challenging for the immune system to control and/or clear (immune "escape") (Dunn et al, 2004a, b;Raval et al, 2014). Cancer immunotherapy attempts to harness the specificity and natural ability of the immune system to recognize and eliminate tumors, while overcoming immunosuppressive barriers present in the tumor microenvironment.…”

“…Today, there are a variety of approaches to elicit antitumor immunity. These approaches include therapeutic cancer vaccines (Cherryholmes et al, 2015;Guo et al, 2013;Knutson and Mittendorf, 2015), antitumor antibodies (Antonioli et al, 2016;Meng et al, 2016b), immune checkpoint blockade (Kakavand et al, 2016;Tang et al, 2016), and adoptive T cell therapy (ACT) (Phan-Lai et al, 2015;Restifo et al, 2012;Yee et al, 2002). In this review only ACT will be discussed.…”