Modulating the tumor immune microenvironment with nanoparticles: A sword for improving the efficiency of ovarian cancer immunotherapy

Abstract

With encouraging antitumor effects, immunotherapy represented by immune checkpoint blockade has developed into a mainstream cancer therapeutic modality. However, only a minority of ovarian cancer (OC) patients could benefit from immunotherapy. The main reason is that most OC harbor a suppressive tumor immune microenvironment (TIME). Emerging studies suggest that M2 tumor-associated macrophages (TAMs), T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSCs), and cancer-associated fibroblasts (CAFs) are enriched in OC. Thus, reversing the suppressive TIME is considered an ideal candidate for improving the efficiency of immunotherapy. Nanoparticles encapsulating immunoregulatory agents can regulate immunocytes and improve the TIME to boost the antitumor immune response. In addition, some nanoparticle-mediated photodynamic and photothermal therapy can directly kill tumor cells and induce tumor immunogenic cell death to activate antigen-presenting cells and promote T cell infiltration. These advantages make nanoparticles promising candidates for modulating the TIME and improving OC immunotherapy. In this review, we analyzed the composition and function of the TIME in OC and summarized the current clinical progress of OC immunotherapy. Then, we expounded on the promising advances in nanomaterial-mediated immunotherapy for modulating the TIME in OC. Finally, we discussed the obstacles and challenges in the clinical translation of this novel combination treatment regimen. We believe this resourceful strategy will open the door to effective immunotherapy of OC and benefit numerous patients.

Keywords: drug delivery system; immunotherapy; nanoparticles; ovarian cancer; tumor immune microenvironment.

Figure 1

Immune cell functions and their interactions in the ovarian cancer tumor microenvironment. M2 TAMs, Tregs, MDSCs, and CAFs suppress the immune response and promote the proliferation, growth, and metastasis of OC. CD8⁺ T cells, NK cells, mature DCs, and M1 TAMs enhanced the immune response and suppressed tumor growth.

Figure 2

Schematic of nanoparticle-mediated immunotherapy regulating the TIME. Nanoparticles are mainly classified as liposomes, micelles, SNPs, and metallic nanoparticles. These nanoparticles have the functions of delivering drugs, delivering nucleic acids, and mediating combination therapy. Based on these functions, nanoparticles can regulate TIME in four ways: (1) mediating PTT and PDT to induce ICD in tumor cells; (2) improving drug targeting to immunosuppressive molecules; (3) targeting Tregs; and (4) targeting TAMs. By reversing the immunosuppressive state of TIME, nanoparticles can enhance the efficacy of immunotherapy such as ICB, ACT, tumor vaccines, and cytokines.