Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages

+ T cell-modulatednHighlight:the anti-cancer effects induced by HCQ are mediated by CD8+ T cell rather than activating T cells directlynHighlight:HCQ did not induce NK cell activation or NK cell-associated anti-cancer effectsnHighlight:HCQ-mediated lung cancer suppression is CD8+ T cell-modulated, but HCQ cannot directly activate CD8+ T cenHighlight:HCQ-induced anti-tumour effect is macrophage-modulatednHighlight:HCQ-induced CD8+ T cell infiltration is macrophage-modulated.nHighlight:HCQ with or without DOX treatment increased inflammatory cytokine expression, such as Ifng, IL12b, IL1b and IL6 (Fig. (Fig.5f),5f), and decreased Tgfb1, IL10 and Vegfa expressionHighlight:HCQ induces CD8+ T cell-based tumour suppression via macrophages in vivonHighlight:TAMs are associated with tumour growth, angiogenesis, metastasis and immune escapenHighlight:HCQ decreased the expression of CD206, which is an M2-like macrophage marker, but increased the expression of MHC II, which is an M1-like macrophage markernHighlight:HCQ switches M2-like TAMs into M1-like macrophages in vitronHighlight:HCQ switches M2-TAMs into M1-like macrophages to enhance CD8+ T cell immuninHighlight:HCQ could reverse the specific role of lysosomes in sequestering chemotherapeutic agents through increasing the pH in lysosomes and could switch M2-TAMs into M1-like macrophages to induce CD8+ T cell infiltration into thnHighlight:HCQ, working as a chemo-enhancer, increased therapeutic efficacy in an immune-mediated manner.nHighlight:CQ, showed a strong ability to increase the sensitivity of cancer cells to chemotherapy in a variety of cancersnHighlight:HCQ is involved in sensitizing cancer cells by decreasing lysosomal acidification, followed by the release of segregated chemotherapeutic drugs from lysosomes to the cytoplasm or nucleus, resulting in increased cytotoxicity of chemotherapynHighlight:HCQ significantly enhanced the efficacy of chemotherapy for NSCLC both in vitro and in vivonHighlight:sensitization effects occur at a low HCQ dosenHighlight:reduced potential systemic toxicitynHighlight:The ability of lysosomes to sequester chemotherapeutic agents is often considered one of the explanations for the low sensitivity of cancer cellsnHighlight:it is necessary to inhibit the lysosomal function of sequestering drugs to enhance the efficacy of chemotherapynHighlight:patient prognosis is often directly correlated with the infiltrating CD8+ T cell number and activation state at the tumour sitesnHighlight:macrophages are required for in CD8+ T cell to induce the anti-tumour ability of HCQnHighlight:HCQ fostered the transition of M2 macrophages to M1 to enhance the anti-tumour effect of CD8+ T cell in NSCLCnHighlight:HCQ reprogrammed M2-TAMs into M1 cells and recruited CD8+ T cell into tumour microenvironment to subject tumour cells to a second hit and induce more potent tumour-killing effects.nHighlight:HCQ, could effectively sensitize NSCLC cells at a low dosenHighlight:HCQ had no toxicitynHighlight:transition of M2-TAMs to M1 macrophages that subsequently recruited and activated CD8+ T cellnHighlight:HCQ as an ideal chemo-sensitizer and immune regulatorn]]>

Picture of About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.


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