Metabolism of Innate Immune Cells in Cancer

Cancer cells possess specific metabolic requirements for their survival, proliferation, and progression. Within a shared microenvironment, immune cells depend on competing metabolic pathways for their development and effector function. As a result, local acidification, hypoxia, and nutrient depletion in the tumor microenvironment can alter the antitumor immune response and even promote resistance to immunotherapies such as immune checkpoint blockade and adoptive cell transfer. Although T cells are the primary effectors of the antitumor response, growing evidence demonstrates that innate immune cells are critical to successful tumor clearance. This review aims to summarize current research related to the innate immune system, metabolism, and cancer. We first discuss the specific metabolic requirements of innate immune cells for immune activation and suppression and conclude by highlighting ongoing clinical applications of these findings.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21124441 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4441 ◽

Cited By ~ 1

Author(s):

Pierpaolo Ginefra ◽

Girieca Lorusso ◽

Nicola Vannini

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Immunotherapy ◽

Cancer Patients ◽

Immune Cells ◽

Adoptive Cell Therapy ◽

Adaptive Immune Response ◽

Immune Checkpoint Blockade ◽

Innate Immune ◽

Innate Immune Cells

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.

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Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development

Frontiers in Immunology ◽

10.3389/fimmu.2021.748325 ◽

2021 ◽

Vol 12 ◽

Author(s):

Greta Volpedo ◽

Thalia Pacheco-Fernandez ◽

Parna Bhattacharya ◽

Timur Oljuskin ◽

Ranadhir Dey ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Immune Cells ◽

Metabolic Pathways ◽

Vaccine Development ◽

Innate Immune ◽

Epigenetic Reprogramming ◽

Sand Fly ◽

Innate Immune Cells ◽

Innate Immune Responses ◽

Inflammatory Monocytes

Leishmaniasis is endemic to the tropical and subtropical regions of the world and is transmitted by the bite of an infected sand fly. The multifaceted interactions between Leishmania, the host innate immune cells, and the adaptive immunity determine the severity of pathogenesis and disease development. Leishmania parasites establish a chronic infection by subversion and attenuation of the microbicidal functions of phagocytic innate immune cells such as neutrophils, macrophages and dendritic cells (DCs). Other innate cells such as inflammatory monocytes, mast cells and NK cells, also contribute to resistance and/or susceptibility to Leishmania infection. In addition to the cytokine/chemokine signals from the innate immune cells, recent studies identified the subtle shifts in the metabolic pathways of the innate cells that activate distinct immune signal cascades. The nexus between metabolic pathways, epigenetic reprogramming and the immune signaling cascades that drive the divergent innate immune responses, remains to be fully understood in Leishmania pathogenesis. Further, development of safe and efficacious vaccines against Leishmaniasis requires a broader understanding of the early interactions between the parasites and innate immune cells. In this review we focus on the current understanding of the specific role of innate immune cells, the metabolomic and epigenetic reprogramming and immune regulation that occurs during visceral leishmaniasis, and the strategies used by the parasite to evade and modulate host immunity. We highlight how such pathways could be exploited in the development of safe and efficacious Leishmania vaccines.

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