Most cancer therapies designate cancer cell death as the therapeutic end goal. Intriguingly, our study reveals that cell death-associated release of PGE2 functions as a mitogen, which recruits quiescent cancer stem cells (CSCs) to repopulate residual tumors [Nature 517, 209–213 (2015)]. PGE2 also acts as an inhibitory DAMP (iDAMP) to dampen dendritic cell activation, and thus T cell priming [Nature Communications 11, 6299 (2020)]. Our most recent study revealed “iDAMP blockade” can convert immune-excluded tumors into inflamed tumors and sensitize them to chemoimmunotherapy [Nature Communications 13, 1487 (2022)]. Studies are underway to translate these concepts into early-phase clinical trials. And to further characterize the immunosuppressive immune and stromal TME [Nature Reviews Urology 19, 515-533 (2022)].