Tumor immunosuppressive environment: effects on tumor-specific and nontumor antigen immune responses

The interactions between cancer cells and host immune cells in tumoral microenvironments create an immunosuppressive network that promotes tumor growth, protects the tumor from immune attack and attenuates the efficacy of immunotherapeutic approaches. The development of immune tolerance becomes predominant in the immune system of patients with advanced-stage tumors. Several mechanisms have been described by which tumors can suppress the immune system, including secretion of cytokines, alterations in antigen-presenting cell subsets, costimulatory and coinhibitory molecule alterations and altered ratios of Tregs to effector T cells. It is well demonstrated that these mechanisms of immunosuppression can impair tumor specific immune responses. However, it is not well established whether this immunosuppressive environment can affect immune responses to nontumor antigens, specifically in regard to priming and the development of memory. The few existing studies indicate that responses to nontumor antigens seem unaffected, although there is still a deep lack of understanding of this phenomenon. This is an important issue regarding patient endurance and quality of life. Here, we review the existing evidence on immunosuppression promoted by tumors, with particular attention to its impact on specific immune responses. Understanding these interactions can help us subvert tumor-induced tolerance and optimize anti-tumor therapy.