Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

Abstract

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.

Targeting TGFβ signal transduction for cancer therapy

“…During tumorigenesis, myeloid cells (including myeloid-derived suppressor cells (MDSCs), macrophages, neutrophils) typically accumulate in the early stage of tumor outgrowth to suppress the T cell response and sustain an immunosuppressive environment. 169 Dendritic cells (DCs) deliver tumor antigens to T cells and natural killer (NK) cells that exert antitumor cytotoxic effects. 170 However, antitumor immune reactions often become suppressed during tumor development; TGFβ can exhibit pivotal immunosuppressive effects on the intrinsic antitumor potential of DCs and NK cells in the TME (Fig.…”

Natural Polysaccharides and Their Derivates: A Promising Natural Adjuvant for Tumor Immunotherapy

“…TAMs exist widely in the anoxic region of TME, and most of them are M2 polarized, resulting in immunosuppressive phenotype and inhibition of T cellmediated adaptive immunity. A series of studies have shown that TAMs affect the therapeutic effect of anti-pd-L1 and anti-CTLA-4 drugs to a great extent, and the curative effect has been observed when traditional immunotherapy were combined with macrophage targeting strategy (Ginefra et al, 2020), but its specific mechanism needs to be further explored.…”

“…In previous studies, pDC is mainly by producing I-IFN to participate in antiviral immunity or other dendritic cell activation; In contrast, cDC can further differentiate through the expression of surface immune receptors, or through crosspresent antigens and other ways to activate anti-tumor specific immune effects (Chan and Housseau, 2008). Thus, the DC can be used to stimulate immature T lymphocytes, which forms a heterogeneous group of specialized antigens presenting cell (APC), and its function is integrated into innate and adaptive immune responses (Ginefra et al, 2020).…”

“…In addition, natural killer cells (NKs) can lyse tumor cells by recognizing tumorderived antigens or cell surface stress molecules (Paul and Lal, 2017). Macrophages can directly participate in tumoricidal activity through antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) (Ginefra et al, 2020).…”

“…Immune cells infiltrate tumors, coevolve and cooperate with tumor cells, create a microenvironment of inflammation and immunosuppression, and promote tumor growth and spread. The innate immune system can directly inhibit tumor progression by participating in the tumor-killing activity, or it can indirectly participate in the anti-tumor process by releasing various inflammatory cytokines and recruiting adaptive immune cells (Fridman et al, 2017;Ginefra et al, 2020).…”