Overall, our data highlight the powerful intrinsic activity of ONCOFID-P-BTM and allow to advance a potential rationale for combinatorial treatments with different drugs: i) targeting the macrophage-CD44 axis or depleting the macrophage/Treg compartment could increase tumor surveillance by CD8+ T cells and make bladder CIS more responsive to ONCOFID-P-BTM treatment. Here, CD44 is linked to neoplasm.