Nanomedicine to modulate immunotherapy in cutaneous melanoma (Review)

Abstract

Cancer immunotherapy has shifted the paradigm in cancer treatment in recent years. Immune checkpoint blockage (ICB), the active cancer vaccination and chimeric antigen receptor (CAR) for T-cell-based adoptive cell transfer represent the main developments, achieving a surprising increased survival in patients included in clinical trials. In spite of these results, the current state-of-the-art immunotherapy has its limitations in efficacy. The existence of an interdisciplinary interface involving current knowledge in biology, immunology, bioengineering and materials science represents important progress in increasing the effectiveness of immunotherapy in cancer. Cutaneous melanoma remains a difficult cancer to treat, in which immunotherapy is a major therapeutic option. In fact, enhancing immunotherapy is possible using sophisticated biomedical nanotechnology platforms of organic or inorganic materials or engineering various immune cells to enhance the immune system. In addition, biological devices have developed, changing the approach to and treatment results in melanoma. In this review, we present different modalities to modulate the immune system, as well as opportunities and challenges in melanoma treatment.

Keywords: cutaneous melanoma; immunotherapy; nano-agents; nanomedicine; nanotechnology.

Figure 1

Schematic of various nanomedicines applied in cancer immunotherapy of cutaneous melanoma. i) Multifunctional CAT-PDL1 liposomes includes CAT that decreases tumor hypoxia decomposing H₂O₂ into O₂ and PDL1 which improves immunotherapeutic effects, promoting CD4⁺and CD8⁺ T cells; ii) PLGA NPs deliver antigenic peptides that target dendritic cells to promote cytotoxic T lymphocyte responses; iii) NPs inhibit IDO and block tryptophan metabolism of cancer cells; iv) NPs block LDH A in tumor cells leading to normal pH; v) NPs cause the translocation of calrecutin and lead to the release of ATP, HMGB1 and HSPs in extracellular environment, inducing ICD of cancer cells; vi) co-polymer NPs aPBAE knock down Cdk5 and cause PD-L1 downregulation via CRISPR-Cas9 genome editing; vii) aCD47@CaCO3 NPs increase the macrophage polarization to M1 phenotype and block the ‘don't eat me’ signal in cancer cells. NPs, nanoparticles; PLGA, poly-lactic-co-glycolic acid; TIME, Tumor Immune Microenvironment; IDO, indoleamine 2,3-dioxygenase; CAT, encapsulated catalase; ICD, Immunogenic cell death; ATP, adenosine triphosphate; HMGB1, high mobility group box 1 protein; HSPc, heat shock proteins.