Immunotherapeutic interventions are effective across a wide range of cancer types, but only a small subset of patients shows clinical response to therapy. Response to immunotherapy has been linked to the presence of a pre-existing ‘’inflamed’’ tumor microenvironment. The contribution of the tumor matrix to the inflamed tumor microenvironment has not been adequately studied. Dendritic cells (DCs) are a heterogeneous population of immune cells that are recognized as key initiators and regulators of T-cell-mediated immunity. Conventional type 1 DCs (cDC1) othwerwise known as Batf3-DC, excel in the activation of cytotoxic lymphocytes including CD8+ T cells (CTLs), as well as innate cells such as NK cells, which are all critical effector cell types in antitumor immunity. Tumor-resident Batf3-lineage dendritic cells (cDC1), although very sparse, are critical for spontaneous anti-tumor responses as well as immunotherapy efficacy. Here we report that versikine, a bioactive proteolytic fragment (matrikine) arising from site-specific N-terminal cleavage of the large matrix proteoglygan versican (VCAN), regulates intratumoral Batf3-DC abundance and function. This observation is consistent with our published reports linking N-terminal VCAN proteolysis with human tumor CD8+ infiltration. Intriguingly, stromal, non-proteolyzed VCAN accumulation is associated with T-cell exclusion, suggesting dichotomous roles between parental VCAN and versikine in T-cell inflammation. To model VCAN proteolysis in the preclinical setting, I use a system of versikine overexpression in tumor cells, showing that versikine localizes in the pericellular matrix, mirroring thus the physiologic site of proteolysis in the human. In this thesis, I demonstrate that versikine modifies the immune milieu of the tumor by boosting Batf3-DC in both solid and hematopoietic tumors. It does not alter tumor-seeding pre-DC differentiation despite robust intratumoral IRF8 induction. Instead, versikine expands and engages an atypical NK subset expressing cytotoxicity receptors, low IFN and high GM-CSF, essential for Batf3-DC survival. Versikine elicits a unique co-stimulatory transcriptional program, distinct from TLR-signatures, that promotes antigen presentation in vitro and in vivo. Moreover, versikine signatures correlate with lung cancer TCGA CD8+ scores. From a translational perspective, versikine synergizes with intratumoral STING agonist therapy and thus, lowers the therapeutic threshold to STING activation in a Batf3-dependent fashion. My results in this Thesis demonstrate tumor T-cell inflammation regulation through matrix remodeling that can be therapeutically exploited.