RE: Biochemist . . .3 Mar 2019 13:51
exactly Crumbs
what most do not consider is the vaccine and the checkpoint is about Reversing "immune suppression" because the cytokines released by an aggressive T cell activates other areas of the immune system that you did not target ... even NK T cells can get excited by a CD4 helper T cell in SCIB1 case Gp100.... in fact even if your cancer does NOT express the cancer cd8 antigen the Cd4 antigen in the vaccine can still reverse the environment ... NK cd4 +
One of the next challenges in cancer immunotherapy is the resistance of tumors to T-cell–based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4+ T cells, whereas activated CD8+ T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice. Mechanistically, imiquimod activated NK cells to kill tumor cells, resulting in release of tumor antigens and induction of tumor-specific CD4+ T cells. These T helper cells provoked a strong induction of CXCL9 and CXCL10 in the tumor environment. Simultaneously, imiquimod induced the expression of the cognate chemokine receptor CXCR3 on peripheral lymphocytes. This ignited intratumoral CD4+ T-cell infiltration and accumulation, which was critical for tumor rejection; CXCR3 blocking antibodies mitigated the clinical response. In the effector phase, NK cell recruitment to tumors and their activation depended on CD4+ T cells. Together, we have uncovered a potent immune axis of tumor-specific CD4+ T cells and NK cells that eliminates escaped MHC-Ilow tumors. Cancer Immunol Res; 5(8); 642–53. ©2017 AACR.
the point of this ,,,,,,,,,,, you have to look at the vaccine and the PD1 as part of an "initiator"
to reverse the escape phase ....
you need to blanket out the T regulatory side of the immune system by Proinflammatory cytokines
and this is all about the Phenotype of the CD4 in the environment ...
TH1 is positive outcome (proinflammatory)
TH2 is a negative outcome (suppression)
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