Our data demonstrate that TREX1 depletion induces tumor cell-intrinsic antiviral signaling that translates into enhanced cell surface expression of MHC-I, as well as secretion of cytokines and chemokines that lead to T cell chemotaxis, suggesting that targeting TREX1 may be a promising strategy to maximize the immunogenicity of chemotherapy or chemoimmunotherapy in “cold” tumors, such as SCLC. This evidence concerns the gene TREX1 and small cell lung carcinoma.