Immune checkpoint blockade (ICB) has rapidly transformed the treatment paradigm for various cancer types. Multiple single or combinations of ICB treatments have been approved by the US Food and Drug Administration, providing more options for patients with advanced cancer. However, most patients could not benefit from these immunotherapies due to primary and acquired drug resistance. Thus, a better understanding of the mechanisms of ICB resistance is urgently needed to improve clinical outcomes. Here, we focused on the changes in the biological functions of CD8+ T cells to elucidate the underlying resistance mechanisms of ICB therapies and summarized the advanced coping strategies to increase ICB efficacy. Combinational ICB approaches and individualized immunotherapies require further in-depth investigation to facilitate longer-lasting efficacy and a more excellent safety of ICB in a broader range of patients.

With the booming development of nanomedicine, mild photothermal therapy (mPTT, 42–45°C) has exhibited promising potential in tumor therapy. Compared with traditional PTT (>50°C), mPTT has less side effects and better biological effects conducive to tumor treatment, such as loosening the dense structure in tumor tissues, enhancing blood perfusion, and improving the immunosuppressive microenvironment. However, such a relatively low temperature cannot allow mPTT to completely eradicate tumors, and therefore, substantial efforts have been conducted to optimize the application of mPTT in tumor therapy. This review extensively summarizes the latest advances of mPTT, including two sections: (1) taking mPTT as a leading role to maximize its effect by blocking the cell defense mechanisms, and (2) regarding mPTT as a supporting role to assist other therapies to achieve synergistic antitumor curative effect. Meanwhile, the special characteristics and imaging capabilities of nanoplatforms applied in various therapies are discussed. At last, this paper puts forward the bottlenecks and challenges in the current research path of mPTT, and possible solutions and research directions in future are proposed correspondingly.