T Cell Exhaustion Fixed
Sept 19, 2024 16:54:21 GMT
Post by Admin on Sept 19, 2024 16:54:21 GMT
One of the concepts you’ll encounter when looking at Immune checkpoint therapy is T cell exhaustion.
www.ncbi.nlm.nih.gov/pmc/articles/PMC9624412/
“Exhausted T cells express a variety of immunoinhibitory molecules, including the molecule PD-1. Following B. burgdorferi infection, we found that PD-1 and its ligand PD-L1 are significantly upregulated on CD4+ T cells and antigen presenting cell subsets, respectively.”
www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1046755/full
“When T cells are continuously stimulated, they become exhausted and continuously overexpress immune checkpoints. In addition, high levels of transforming growth factor β (TGF-β) and the angiogenesis-promoting molecule VEGF-A regulate the expression of immune checkpoint molecules on CD8+T cells in the TME “
These PD1 , VEGF, TNF etc. pathways can all be manipulated so T cells don’t become “Exhausted”. The T cells aren’t really tired, they have just been shut off.
I looked at a lot of different potential treatments and the two that stand out are Fucoidan and Solamargine because they not only work on the interior of a cell to restore apoptosis they also correct cytokine levels and block pathways that cause T cell exhaustion.
pubs.rsc.org/en/content/articlelanding/2024/fo/d3fo04807a
“These modulations improved the function of effector T cells and suppressed Treg cell production. Thus, our findings suggest that fucoidan combined with the anti-PD-1 monoclonal antibody may be a novel strategy to sensitize breast cancer patients to anti-PD-1 monoclonal antibody immunotherapy”
pubmed.ncbi.nlm.nih.gov/36898463/
“Structural characterization of a sulfated polysaccharide from Ishige okamurae and its effect on recovery from immunosuppression”
“Chemical and spectroscopic analyses demonstrated that IOY was a fucoidan”
“Furthermore, IOY had a significant effect on hematopoietic function recovery and promoted the secretion of interleukin-2 (IL-2) and tumor necrosis factor (TNF-α). Notably, IOY reversed CD4+ and CD8+ T cell reduction and improved immune response.”
pubmed.ncbi.nlm.nih.gov/15336528/
“Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells”
“A loss of TNF receptors expression has been found in advanced lung cancers, and human A549 lung adenocarcinoma cells are resistant to the cytotoxic effects of TNF-alpha and cisplatin.”
“In addition, release of cytochrome c from mitochondria, down-expression of Bcl-2 and Bcl-x(L), up-regulation of Bax, and caspase-9 activities were observed in SM-treated A549 cells. Combinational treatment of SM and cisplatin synergistically enhanced caspase-8, -9, and -3 activities in A549 cells. Thus, SM sensitizes A549 cells through TNFRs and mitochondria-mediated pathways”
The combination of solamargine and fucoidan takes care of the issue of T cell exhaustion as well as restoring apoptosis by downregulating Bcl-2.
A major player in keeping the immune system from killing the infection are the Bcl-2 and BAX proteins inside the infected cells. Bcl-2 is anti-apoptotic and BAX is pro-apoptotic. These infections increase the level of Bcl-2 and decrease the level of BAX so that the immune system can’t kill the infected cells.
pubmed.ncbi.nlm.nih.gov/14586269/
“Apoptosis in Lyme borreliosis”
“The concentration of bcl-2 was elevated significantly in all groups in examination 1 and dropped during treatment, remaining significantly increased in group I. “
Bcl-2 is explained here;
bartonella.freeforums.net/thread/136/bcl-2
~d
www.ncbi.nlm.nih.gov/pmc/articles/PMC9624412/
“Exhausted T cells express a variety of immunoinhibitory molecules, including the molecule PD-1. Following B. burgdorferi infection, we found that PD-1 and its ligand PD-L1 are significantly upregulated on CD4+ T cells and antigen presenting cell subsets, respectively.”
www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1046755/full
“When T cells are continuously stimulated, they become exhausted and continuously overexpress immune checkpoints. In addition, high levels of transforming growth factor β (TGF-β) and the angiogenesis-promoting molecule VEGF-A regulate the expression of immune checkpoint molecules on CD8+T cells in the TME “
These PD1 , VEGF, TNF etc. pathways can all be manipulated so T cells don’t become “Exhausted”. The T cells aren’t really tired, they have just been shut off.
I looked at a lot of different potential treatments and the two that stand out are Fucoidan and Solamargine because they not only work on the interior of a cell to restore apoptosis they also correct cytokine levels and block pathways that cause T cell exhaustion.
pubs.rsc.org/en/content/articlelanding/2024/fo/d3fo04807a
“These modulations improved the function of effector T cells and suppressed Treg cell production. Thus, our findings suggest that fucoidan combined with the anti-PD-1 monoclonal antibody may be a novel strategy to sensitize breast cancer patients to anti-PD-1 monoclonal antibody immunotherapy”
pubmed.ncbi.nlm.nih.gov/36898463/
“Structural characterization of a sulfated polysaccharide from Ishige okamurae and its effect on recovery from immunosuppression”
“Chemical and spectroscopic analyses demonstrated that IOY was a fucoidan”
“Furthermore, IOY had a significant effect on hematopoietic function recovery and promoted the secretion of interleukin-2 (IL-2) and tumor necrosis factor (TNF-α). Notably, IOY reversed CD4+ and CD8+ T cell reduction and improved immune response.”
pubmed.ncbi.nlm.nih.gov/15336528/
“Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells”
“A loss of TNF receptors expression has been found in advanced lung cancers, and human A549 lung adenocarcinoma cells are resistant to the cytotoxic effects of TNF-alpha and cisplatin.”
“In addition, release of cytochrome c from mitochondria, down-expression of Bcl-2 and Bcl-x(L), up-regulation of Bax, and caspase-9 activities were observed in SM-treated A549 cells. Combinational treatment of SM and cisplatin synergistically enhanced caspase-8, -9, and -3 activities in A549 cells. Thus, SM sensitizes A549 cells through TNFRs and mitochondria-mediated pathways”
The combination of solamargine and fucoidan takes care of the issue of T cell exhaustion as well as restoring apoptosis by downregulating Bcl-2.
A major player in keeping the immune system from killing the infection are the Bcl-2 and BAX proteins inside the infected cells. Bcl-2 is anti-apoptotic and BAX is pro-apoptotic. These infections increase the level of Bcl-2 and decrease the level of BAX so that the immune system can’t kill the infected cells.
pubmed.ncbi.nlm.nih.gov/14586269/
“Apoptosis in Lyme borreliosis”
“The concentration of bcl-2 was elevated significantly in all groups in examination 1 and dropped during treatment, remaining significantly increased in group I. “
Bcl-2 is explained here;
bartonella.freeforums.net/thread/136/bcl-2
~d