In conclusion, TCAs, exemplified by imipramine, have been revealed herein to elevate levels of ostensibly immunostimulatory autophagy in cancer cells and to reprogram immunosuppressive macrophages in the TME to express chemokines that attract otherwise rare CD8 T cells, which are expanded and activated by the inclusion of VEGF pathway inhibitors and further sustained by immune-checkpoint blockade, collectively contributing to the significant therapeutic efficacy of this innovative mechanism-guided therapeutic strategy (Figure 7P). Here, VEGFA is linked to cancer.