Immunoregulatory pathways following strong inflammatory processes markedly impair CD4+ T cell responses.

As the research and use of immunotherapies is expanding, isolating ideal combinational strategies has become the next goal for many investigators. Vaccine therapies are also becoming one of the many combinational strategies being utilized in conjunction with immunostimulatory antibodies such as checkpoint blockade or adjuvants to stimulate immune responses. Here we review aspects of the immune responses that remain to be considered for designing future targeted therapies given the recent findings of the role of out of order T cell activation signaling. Specifically, we review some considerations in generating primary T cell responses under conditions of strong immunostimulatory signals based on recent studies completed by our group and others.