Triple-negative breast cancer(TNBC)due to lack of clear target and notorious“cold”tumor microenvironment(TME)is one of the most intractable and lethal malignancies.Tuning“cold”TME into“hot”becomes an emerging th...Triple-negative breast cancer(TNBC)due to lack of clear target and notorious“cold”tumor microenvironment(TME)is one of the most intractable and lethal malignancies.Tuning“cold”TME into“hot”becomes an emerging therapeutic strategy to TNBC.Herewith,we report that integrin-targeting micellar gemcitabine and paclitaxel(ATN-mG/P,ATN sequence:Ac-PhScNK-NH2)cooperating with polymersomal CpG(NanoCpG)effectively“heated up”and treated TNBC.ATN-mG/P exhibited greatly boosted apoptotic activity in 4T1 cells,induced potent immunogenic cell death(ICD),and efficiently stimulated maturation of bone marrow-derived dendritic cells(BMDCs).Remarkably,in a postoperative TNBC model,ATN-mG/P combining with NanoCpG promoted strong anti-cancer immune responses,showing a greatly augmented proportion of mature DCs and CD8^(+)T cells while reduced immune-suppressive myeloid-derived suppressor cells(MDSCs)and regulatory T cells(T_(reg)),which led to complete inhibition of lung metastasis and 60%mice tumor-free.The co-delivery of gemcitabine and paclitaxel at desired ratio in combination with NanoCpG provides a unique platform for potent chemoimmunotherapy of“cold”tumors like TNBC.展开更多
基金This work is supported by research grants from the National Natural Science Foundation of China(NSFC 52033006).
文摘Triple-negative breast cancer(TNBC)due to lack of clear target and notorious“cold”tumor microenvironment(TME)is one of the most intractable and lethal malignancies.Tuning“cold”TME into“hot”becomes an emerging therapeutic strategy to TNBC.Herewith,we report that integrin-targeting micellar gemcitabine and paclitaxel(ATN-mG/P,ATN sequence:Ac-PhScNK-NH2)cooperating with polymersomal CpG(NanoCpG)effectively“heated up”and treated TNBC.ATN-mG/P exhibited greatly boosted apoptotic activity in 4T1 cells,induced potent immunogenic cell death(ICD),and efficiently stimulated maturation of bone marrow-derived dendritic cells(BMDCs).Remarkably,in a postoperative TNBC model,ATN-mG/P combining with NanoCpG promoted strong anti-cancer immune responses,showing a greatly augmented proportion of mature DCs and CD8^(+)T cells while reduced immune-suppressive myeloid-derived suppressor cells(MDSCs)and regulatory T cells(T_(reg)),which led to complete inhibition of lung metastasis and 60%mice tumor-free.The co-delivery of gemcitabine and paclitaxel at desired ratio in combination with NanoCpG provides a unique platform for potent chemoimmunotherapy of“cold”tumors like TNBC.
