Dendritic cells (DCs) control the activation and infiltration of CD8+ T cells within the tumor microenvironment (TME). This process supports the immune control of tumors and explain the efficiency of immune checkpoint blockade immunotherapy. However, DC infiltration in tumors is typically low and controlled by immunosuppressive mechanisms activated by tumors. Here, the inventors propose a new approach to promote DC infiltration in solid tumors, increase antitumor specific T cell responses and achieve the activation of anti-tumor immunity. This approach is based on the intra-tumoral engraftment within solid tumors of autologous engineered stromal cells delivering factors favoring DC infiltration. Specifically, fibroblasts engineered to express the membrane bound form of FLT3L (eMSC-FLT3L) induce anti-tumor
immunity when combined with adjuvant like the poly(I:C) double stranded RNA mimic. DC infiltration, T cell activation and the therapeutic anti-tumor effect is uniquely dependent on the presence of both eMSC-FLT3L and poly(I:C). Mechanistic experiments demonstrate that poly(I:C)-induced chemokine (CXCR3 and CCR5 ligands) are required for the therapeutic effect of eMSC-FLT3L + poly(I:C). Finally, stromal cell-based delivery of chemokines (CXCR3, CCR5 or XCR1 ligands) together with membrane bound form of FLT3L is sufficient to activate anti-tumor immunity in the absence of poly(I:C). Altogether, these data support the therapeutic potential of intra-tumoral engraftment of autologous mesenchymal stromal cells to induce anti-tumor immunity.