This might be, as the authors suggest, because these ‘‘self’’-specific CD4+ T cells have more antitumor activity independent of CD8+ T cells and B cells. Alternatively, these data are predicted by the threshold hypothesis of Peter Bretscher [23], where low levels of T-cell help promote

Th1 responses while high levels of T-cell help promote a Th2/antibody response at the expense of tumor-destructive cell-mediated immunity [23]. Given that T-cell help promotes different types of immunity and that Th1/CTL cell-mediated immunity is the most useful for tumor elimination, not all types or Ibrutinib in vitro levels of T-cell help will be beneficial in tumor elimination. Examination of the IgG subclass induced in WT versus GUCY2C−/− mice immunized with GUCY2C-S1 may help resolve these possibilities as the subclass is directly determined by the type of T-cell helper response generated (Th1/Th2 etc.). In addition, the efficacy of a particular foreign helper epitope might not be universal. Cross-reactivity of the relevant TCR to an environmental antigen mimic might set the CD4+ T-cell response to exogenous helper determinants into a regulatory/suppressive mode in some individuals. Given the above possibilities, it will be important not to abandon this well-grounded approach of linked foreign

epitopes in cancer vaccines to boost the immune response should initial clinical evaluation suggest a lack of efficacy [24]. Determination of the appropriate Selleckchem NVP-AUY922 helper epitope dose and the consequent level, type, and frequency of restimulation of T-cell help will be needed to take full advantage of this pathway. Determining these parameters for optimal exogenous T-cell help would be anticipated to contribute not only to protection against subsequent tumors but also destruction of already established tumors [25]. It is perhaps instructive that the value in tumor treatment of providing foreigner helper epitopes or blocking coinhibitors (CTLA-4 and PD-1) [26] are both direct predictions ifoxetine from earlier efforts to generate a broad theoretical understanding of the

central problem in immunology, the self/nonself discrimination [27-29] (reviewed in [30]). Although the importance of broad theories in immunology has often been questioned [31], the current progress in tumor immunotherapy provides a testament to their value. The author is supported by a senior scholar award from Alberta Innovates Health Solutions. I thank Dawne Colwell for assistance with artwork. The author declares no financial or commercial conflict of interest. “
“Citation Loureiro B, Oliveira LJ, Favoreto MG, Hansen PJ. Colony-stimulating factor 2 inhibits induction of apoptosis in the bovine preimplantation embryo. Am J Reprod Immunol 2011; 65: 578–588 Problem  Addition of colony-stimulating factor 2 (CSF2) to culture medium increases post-transfer survival of bovine embryos.