Combination of cancer immunotherapy with clinically available drugs that can block immunosuppressive cells

Abstract

Although cancer immunotherapy, which is able to target specifically cancer cells without detrimental effects to normal cell functions, would serve as an ideal therapeutic modality, most of the randomized clinical trials of cancer immunotherapy have not demonstrated a meaningful survival benefit to cancer patients over preexisting therapeutic modalities. Due to the discrepancy between the impressive preclinical results and the limited clinical results, the cancer immunotherapy is not accepted generally as a standard therapy for cancers. A variety of immune escape mechanisms are thought to be involved in this ineffectiveness of cancer immunotherapy. Therefore, elimination of immunosuppressive activities in tumor microenvironment will enhance the effectiveness of cancer immunotherapy, which is currently focused on activation of tumor-specific immune responses. Since there are now increasing evidences showing that many cytotoxic anticancer drugs including targeted agents given in lower-than-therapeutic doses have not only the ability to eliminate tumor cells but can also block the immunosuppressive activities in tumor microenvironments and consequently favor the development of anticancer immune responses, clinically available drugs can be considered for their rapid application to cancer immunotherapies to enhance the efficacy of cancer immunotherapies with marginal effects on cancer treatment.

Mreg Activity in Tumor Response to Photodynamic Therapy and Photodynamic Therapy-Generated Cancer Vaccines

“…Dampening immunosuppressive actions of Tregs and Mregs is now considered a key approach for securing a successful outcome of tumor immunotherapy [3]. A number of strategies for restraining Mreg activity have been tested in pre-clinical and clinical studies [26].…”

“…However, lasting therapeutic responses were still remaining largely unattainable and it was only recently established that the attainment of complete tumor elimination requires maintaining the mobilized tumor-specific T cells and immune effectors in the activated state by preventing that they are rendered tolerant or exhausted [2]. Hence it has become clear that for achieving a decisive success with cancer immunotherapy it is necessary to relieve the inhibitory effects of immunoregulatory mechanisms (developed to assure self-tolerance) that are manifested as either immunoregulatory cell activity or through inhibitory intercellular signals mediated by multiple negative checkpoint regulators [3,4]. …”

Immunoregulatory Cell Depletion Improves the Efficacy of Photodynamic Therapy-Generated Cancer Vaccines

“…Strength and duration of antitumor immune response can be actively attenuated by negative regulatory immune cell populations [ 14 ]. It has become increasingly clear that the activity of these immunoregulatory cells physiologically engaged in the maintenance of immunological self-tolerance is a major barrier to effective tumor immunotherapy [ 14 , 15 , 16 ]. Tumors can recruit and activate suppressive or regulatory cells from both adaptive and innate arms of the immune system.…”

Traditional Oriental Herbal Medicine and Natural Killer Cells for Cancer Patients: A Systematic Review and Meta-analysis

“…Current conventional immunotherapy and targeted therapy, which aim to destroy cancer cells without damaging normal cell function, have not demonstrated a meaningful survival benefit to cancer patients without inducing adverse effects (Kim et al, ). Considering this understanding of the limitations of current immunotherapy and targeted therapy, the results of our review provide insight into the use of HM as a potential adjunct immunotherapy.…”