Optimal regulation of tumour-associated neutrophils in cancer progression

Reyes, Aurelio A. de los; Kim, Yangjin

doi:10.1098/rsos.210705

Cited by 13 publications

(3 citation statements)

References 174 publications

(200 reference statements)

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“…Contrarily, N2 neutrophils promote cancer cell proliferation, angiogenesis, and immune evasion [623,624]. It has been confirmed that IFN-I polarizes neutrophils toward the antitumor N1 phenotype, while TGF-β drives the polarization toward the protumor N2 phenotype [625][626][627][628][629]. The N1/N2 nomenclature for TAN is inspired by the classification of activation states observed in TAM.…”

Section: Neutrophil-targeted Therapiesmentioning

confidence: 99%

Exploiting innate immunity for cancer immunotherapy

Yi,

Li,

Niu

et al. 2023

Mol Cancer

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Immunotherapies have revolutionized the treatment paradigms of various types of cancers. However, most of these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory signaling with bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although these agents have already achieved great success, only a tiny percentage of patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined by multiple components in the tumor microenvironment beyond adaptive immunity. Cells from the innate arm of the immune system, such as macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, natural killer cells, and unconventional T cells, also participate in cancer immune evasion and surveillance. Considering that the innate arm is the cornerstone of the antitumor immune response, utilizing innate immunity provides potential therapeutic options for cancer control. Up to now, strategies exploiting innate immunity, such as agonists of stimulator of interferon genes, CAR-macrophage or -natural killer cell therapies, metabolic regulators, and novel immune checkpoint blockade, have exhibited potent antitumor activities in preclinical and clinical studies. Here, we summarize the latest insights into the potential roles of innate cells in antitumor immunity and discuss the advances in innate arm-targeted therapeutic strategies.

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Section: Neutrophil-targeted Therapiesmentioning

confidence: 99%

Exploiting innate immunity for cancer immunotherapy

Yi,

Li,

Niu

et al. 2023

Mol Cancer

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“…All this makes TGF-β an emerging target in cancer therapy [ 245 ]. De los Reyes et al developed a mathematical approach to optimize the N2 to N1 transition in cancer patients using TGF-β inhibitors and IFN-β, and their results were promising enough to be used in clinical research [ 246 ]. Several in vitro and in vivo studies supported the mathematical models and demonstrated the potential of modulating the neutrophil functional state or inhibiting neutrophil recruitment to the tumor microenvironment using TGF-β inhibitors [ 243 , 247 , 248 , 249 ].…”

Section: Neutrophil In Cancer Therapy: Potential Strategiesmentioning

confidence: 99%

Diverse Neutrophil Functions in Cancer and Promising Neutrophil-Based Cancer Therapies

Sounbuli

Миронова

Alekseeva

2022

IJMS

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Neutrophils represent the most abundant cell type of leukocytes in the human blood and have been considered a vital player in the innate immune system and the first line of defense against invading pathogens. Recently, several studies showed that neutrophils play an active role in the immune response during cancer development. They exhibited both pro-oncogenic and anti-tumor activities under the influence of various mediators in the tumor microenvironment. Neutrophils can be divided into several subpopulations, thus contradicting the traditional concept of neutrophils as a homogeneous population with a specific function in the innate immunity and opening new horizons for cancer therapy. Despite the promising achievements in this field, a full understanding of tumor–neutrophil interplay is currently lacking. In this review, we try to summarize the current view on neutrophil heterogeneity in cancer, discuss the different communication pathways between tumors and neutrophils, and focus on the implementation of these new findings to develop promising neutrophil-based cancer therapies.

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“…The optimal control theory (OCT) is an essential tool frequently used to solve a wide range of optimization problems for dynamical systems including vaccine allocation problems in public health [1,4,7,9,15,17,22,27,30,35,37,41,42,44]. Probably one of the most relevant issues when solving optimization problems via OCT is the choice of the performance criterion, that is the objective functional to be minimized or maximized [11,20,16,26,43].…”

Section: Introductionmentioning

confidence: 99%

Optimal vaccination strategies for a heterogenous population using multiple objectives: The case of L1− and L2−formulations

Saldaña

Kebir

Camacho-Gutíerrez³

et al. 2023

Preprint

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The choice of the objective functional in optimization problems coming from biomedical and epidemiological applications plays a key role in optimal control outcomes. In this study, we investigate the role of the objective functional on the structure of the optimal control solution for an epidemic model that includes a core group with higher sexual activity levels than the rest of the population. An optimal control problem is formulated to find a targeted vaccination program able to control the spread of the infection with minimum vaccine deployment. Both $L_{1}-$ and $L_{2}-$objectives are considered as an attempt to explore the trade-offs between control dynamics and the functional form characterizing optimality. Our results show that the optimal vaccination policy for both the $L_{1}-$ and the $L_{2}-$formulation share one important qualitative property, that is, immunization of the core group should be prioritized by policymakers to achieve a fast reduction of the epidemic. Nevertheless, quantitative aspects of this result can be significantly affected depending on the objective weightings. Overall, our results suggest that the optimal control profiles are reasonably robust with respect to the $L_{1}-$ or $L_{2}-$formulation when the monetary cost of the vaccination policy is substantially lower than the cost associated with the disease burden but if this is not the case the optimal control profiles can be radically different for each formulation.

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Optimal regulation of tumour-associated neutrophils in cancer progression

Cited by 13 publications

References 174 publications

Exploiting innate immunity for cancer immunotherapy

Exploiting innate immunity for cancer immunotherapy

Diverse Neutrophil Functions in Cancer and Promising Neutrophil-Based Cancer Therapies

Optimal vaccination strategies for a heterogenous population using multiple objectives: The case of L1− and L2−formulations

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