Search

Colorectal cancer (CRC) is considered as the second most common cancer worldwide. For the past few years, the role of immunotherapy has been extensively studied and it has been demonstrated that its related approaches, such as programmed death-1 (PD-1) inhibitors, are promising. In addition to identifying molecular characteristics of tumor cells, recent studies are mainly focused on the profiling of tumor microenvironment. Dissecting immune status of a tumor is interesting, since development of a tumor is associated with deficiencies relate to immune defense, immune surveillance and immune hemostasis. In this review, we discuss main obstacles of immunotherapy including immunosuppressive niche and low immunogenicity of CRC as well as reviewing current achievements in immunotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cancer immunotherapy suppresses and destroys tumors by re-activating and sustaining the tumor-immune process, and thus improving the immune response of the body to the tumor. Immunotherapeutic strategies are showing promising results in pre-clinical and clinical trials, however, tumor microenvironment (TME) is extremely immunosuppressive. Thus, their translation from labs to clinics still faces issues. Recently, nanomaterial-based strategies have been developed to modulate the TME for robust immunotherapeutic responses. The combination of nanotechnology with immunotherapy potentiates the effectiveness of immunotherapy by increasing delivery and retention, and by reducing immunomodulation toxicity. This review aims to highlight the barriers offered by TME for hindering the efficiency of immunotherapy for cancer treatment. Next, we highlight various nano-carriers based strategies for modulating those barriers for achieving better therapeutic efficacy of cancer immunotherapy with higher safety. This review will add to the body of scientific knowledge and will be a good reference material for academia and industries.

Simple Summary: Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with dismal survival and poor response to conventional therapies. Therefore, the development of immunotherapy for GBM treatment is necessary. However, the rigorous immunosuppression in the GBM-microenvironment (GME) is a crucial impediment for GBM immunotherapy. The adenosinergic pathway (AP) is a major player in suppressing antitumor immune responses in the GME. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. Tumor cells metabolize pro-inflammatory ATP to anti-inflammatory adenosine using CD39 and CD73 enzymes. Adenosine suppresses immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in the GBM showed promising results in reinvigorating antitumor responses and overriding chemoresistance. We suggest that future clinical studies should consider this pathway in combination therapies along with other immunotherapeutic approaches. Brain tumors comprise different types of malignancies, most of which are originated from glial cells. Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with a poor response to conventional therapies and dismal survival rates (15 months) despite multimodal therapies. The development of immunotherapeutic strategies seems to be necessary to enhance the overall survival of GBM patients. So far, the immunotherapies applied in GBM had promising results in the primary phases of clinical trials but failed to continue their beneficial effects in later phases. GBM-microenvironment (GME) is a heterogenic and rigorously immunosuppressive milieu wrapping by an impenetrable blood-brain barrier. Hence, in-depth knowledge about the dominant immunosuppressive mechanisms in the GME could foster GBM immunotherapy. Recently, the adenosinergic pathway (AP) is found to be a major player in the suppression of antitumor immune responses in the GME. Tumor cells evolve to metabolize pro-inflammatory ATP to anti-inflammatory adenosine. Adenosine can suppress immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in GBM showed promising results in reinvigorating antitumor responses, overriding chemoresistance, and increasing survival. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. We suggest that future clinical studies should consider this pathway in their combination therapies along with other immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]