Colorectal　cancer　(CRC),　mostly　categorized　as　a　low　immunogenic　microsatellite-stable　phenotype　bearing　complex　immunosuppressive　tumor　microenvironment　(TME),　is　highly　resistant　to　immunotherapy.　Seeking　safe　and　efficient　alternatives　aimed　at　modulating　tumor　immunosuppressive　TME　to　improve　outcome　of　CRC　is　highly　anticipated　yet　remains　challenging.　Methods:　Enlightened　from　the　drug　complementary　art　in　traditional　Chinese　medicine,　we　designed　a　self-assembled　nanomedicine　(termed　LNT-UA)　by　the　natural　active　ingredients　of　ursolic　acid　(UA)　and　lentinan　(LNT)　through　a　simple　nano-precipitation　method,　without　any　extra　carriers,　for　CRC　immunotherapy.　Results:　UA　induces　immunogenic　cell　death　(ICD),　while　LNT　further　promotes　dendritic　cell　(DC)　maturation　and　repolarizes　tumor-associated　macrophage　(TAM)　from　a　protumorigenic　M2　to　an　antitumor　M1　phenotype.　Co-delivery　of　UA　and　LNT　by　LNT-UA　effectively　reshapes　the　immunosuppressive　TME　and　mobilizes　innate　and　adaptive　immunity　to　inhibit　tumor　progression　in　the　CT26　CRC　tumor　model.　Following　the　principle　of　integrative　theoretical　system　of　traditional　Chinese　medicine　(TCM)　on　overall　regulation,　the　further　combination　of　LNT-UA　and　anti-CD47　antibody　(aCD47)　would　reinforce　the　antitumor　immunity　by　promoting　phagocytosis　of　dying　tumor　cells　and　tumor-associated　antigens　(TAAs),　leading　to　effective　suppression　of　both　primary　and　distant　tumor　growth　with　2.2-fold　longer　of　median　survival　time　in　the　bilateral　tumor　model.　Most　notably,　this　combination　effect　is　also　observed　in　the　spontaneous　CRC　model　induced　by　chemical　carcinogens,　with　much　less　and　smaller　size　of　tumor　nodules　after　sequential　administration　of　LNT-UA　and　aCD47　through　gavage　and　intraperitoneal　injection,　respectively.　Conclusions:　This　study　provides　a　promising　self-assembled　traditional　Chinese　nanomedicine　to　improve　immunotherapy　for　CRC,　which　might　be　applicable　for　future　clinical　translation.