**4. Conclusion**

ICT-mediated immunotherapy has attracted extensive research interest and pioneered a new paradigm for cancer treatment over the past decades. The final goal of ICT is to induce a robust antitumor response by interfering immunosuppressive TMEs while alleviating side effects. Various strategies have been investigated for enhancing efficacy of ICT, including nanotechnology-mediated targeted delivery

of ICIs, regulation of the immunosuppressive TME, and combination therapies. Despite substantial progress, the issues of immune-related adverse events (irAEs) and therapeutic resistance may lead to the failure of therapy and even patient mortality in some cases. Biomarkers can be employed to predict the efficacy of ICI treatment and irAEs by distinguishing responders and non-responders, which would promote patient selection and decision-making. Abundant opportunities remain in ICT for maximizing therapeutic effects, improving safety profiles, and reducing recurrence. We believe that expanding the understanding of immune checkpoint biology and nanotechnology will improve the efficacy of current ICT and continuously contribute to the next generation of novel immunotherapy for clinical translation.
