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Conventionally, surgical therapy, radiotherapy and chemotherapy have been applied widely to treat cancer.Meanwhile, immunotherapy has emerged as an attractive alternative therapy for those which cannot be treated by the conventional modalities.However, recent progress in tumor immunology has revealed that tumors can generate immunologically restrained milieu during the process of their growth, which facilitates the escape of tumors from host immune systems.In the study, we investigated the potential benefits of co-delivering Paclitaxel (PTX) and interleukin-2 (IL-2) through a Thermosponge Nanoparticle platform (TSN) to modulate the tumor microenvironment.TSNs releasing PTX and IL-2 in a sustained fashion can significantly prolong mice survival, delay tumor growth and inhibit tumor metastasis in the subcutaneous and metastatic melanoma models,respectively.To elucidate the immunologic mechanisms behind the synergistic therapeutic effects, the immunocytes were collected from spleens, draining lymph nodes and tumor tissues and then evaluated by flow cytometer.We demonstrated the efficacy of chemotherapy combining with immunotherapy via TSNs as vector resulted from reshaping the tumor microenvironment.