“…Trabectidin, a tetrahydroisoquinoline alkaloid that was initially isolated from the Caribbean tunicate Ecteinascida turbinata with the name of ET-743 [198,199], has been the first marine-derived anti-neoplastic drug approved for the treatment of advanced soft tissue sarcoma and, in combination with pegylated liposomal doxorubicin, for the treatment of patients with relapsed platinum-sensitive ovarian cancer. The alkaloid besides the cytotoxic effect has immunomodulatory activity on several cell types of the microenvironment [200]. Several studies have also underlined that Trabectedin is an immunomodulatory drug with potential use in enhancing the therapeutic response to checkpoint inhibitor-based immunotherapy and in overcoming chemoimmune resistance [200,201] Stimulation of cytokine production [193,194] Abbreviations: AP-1, activator protein 1; NF-kB, nuclear factor kappa of activated B cells; CD, cluster of differentiation; IL-8, interleukin 8; NK, natural killer; Th1, T helper 1; Th2, T helper 2; DC, dendridic cell; PCK, Protein kinase C.…”