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Simple Summary: Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy, and it has greatly expanded our knowledge of anticancer immunity and has introduced breakthroughs in cancer therapy. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. This review provides an overview of recent advances in cellular and molecular factors within the tumor microenvironment (TME) to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies for cancer immunotherapy. The in-depth exploration of complexity within the TME allows for the improvement of therapeutic efficacy and highlights its contribution to cancer immunotherapy. Immune checkpoints play critical roles in the regulation of T-cell effector function, and the effectiveness of their inhibitors in cancer therapy has been established. Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy in general and cancer immunotherapy in particular. Immunotherapy has been indicated to reinvigorate antitumor T-cell activity and dynamically modulate anticancer immune responses. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. Overall, immunotherapy involves a certain degree of uncertainty and complexity. Research on the exploration of cellular and molecular factors within the tumor microenvironment (TME) aims to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies involving the specific targeting of the TME for cancer immunotherapy. The combination of this approach with other types of treatment, including immune checkpoint blockade therapy involving multiple agents, most of the responses and effects in cancer therapy could be significantly enhanced, but the appropriate combinations have yet to be established. Moreover, the in-depth exploration of complexity within the TME allows for the exploration of pathways of immune dysfunction. It may also aid in the identification of new therapeutic targets. This paper reviews recent advances in the improvement of therapeutic efficacy on the immune context of the TME and highlights its contribution to cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer immunotherapy is a breakthrough in cancer treatment. Unfortunately, despite the encouraging results in clinical treatment, cancer immunotherapy such as CAR-T, PD-1 still faces lots of challenges. Therefore, it is necessary to develop new methods to improve the effectiveness and safety of tumor immunotherapy. In recent years, cell membrane-coated nanomaterial is one of the most promising drug delivery systems and is receiving a great deal of attention due to its naturally biocompatible characteristics. This review summarizes the latest research progress, the advantages, the disadvantages, and the application of immunocyte membrane-coated nanoparticles in cancer immunotherapy. Despite the advances in surface bioconjugation of synthetic nanoparticles for targeted drug delivery, simple biological functionalization is still insufficient to replicate complex intercellular interactions naturally. Therefore, these foreign nanoparticles are inevitably exposed to the immune system, which results in phagocytosis by the reticuloendothelial system and thus, loss of their biological significance. Immunocyte membranes play a key role in intercellular interactions, and can protect foreign nanomaterials as a natural barrier. Therefore, biomimetic nanotechnology based on cell membranes has developed rapidly in recent years. This paper summarizes the development of immunocyte membrane-coated nanoparticles in the immunotherapy of tumors. We will introduce several immunocyte membrane-coated nanocarriers and review the challenges to their large-scale preparation and application. [ABSTRACT FROM AUTHOR]

Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans. [ABSTRACT FROM AUTHOR]