Targeting macrophages in cancer immunotherapy

Duan, Zhiqing; Luo, Yunping

doi:10.1038/s41392-021-00506-6

Cited by 335 publications

(223 citation statements)

References 283 publications

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“…The role of immunotherapy is to enhance or inhibit the immune system to fight against diseases, and kill cancer cells and tumor tissues relying on the immune function. Recently, scientists found that targeting macrophages may be a potential treatment and summarized the role of macrophages in tumors 140 . However, tumor heterogeneity creates a major challenge with immunotherapy, including low response rate and drug resistance limitations.…”

Section: Advances Of Ir-seq In Clinical Applicationmentioning

confidence: 99%

The methods and advances of adaptive immune receptors repertoire sequencing

Pan

Tang

et al. 2021

Theranostics

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The adaptive immune response is a powerful tool, capable of recognizing, binding to, and neutralizing a vast number of internal and external threats via T or B lymphatic receptors with widespread sets of antigen specificities. The emergence of high-throughput sequencing technology and bioinformatics provides opportunities for research in the fields of life sciences and medicine. The analysis and annotation for immune repertoire data can reveal biologically meaningful information, including immune prediction, target antigens, and effective evaluation. Continuous improvements of the immunological repertoire sequencing methods and analysis tools will help to minimize the experimental and calculation errors and realize the immunological information to meet the clinical requirements. That said, the clinical application of adaptive immune repertoire sequencing requires appropriate experimental methods and standard analytical tools. At the population cell level, we can acquire the overview of cell groups, but the information about a single cell is not obtained accurately. The information that is ignored may be crucial for understanding the heterogeneity of each cell, gene expression and drug response. The combination of high-throughput sequencing and single-cell technology allows us to obtain single-cell information with low-cost and high-throughput. In this review, we summarized the current methods and progress in this area.

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Section: Advances Of Ir-seq In Clinical Applicationmentioning

confidence: 99%

The methods and advances of adaptive immune receptors repertoire sequencing

Pan

Tang

et al. 2021

Theranostics

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“…Hypoxia induces CXCL12 and CXCR4 expression, which modulate the migration of monocytes, monocyte-derived macrophages, and TAMs ( 65 ) ( Figure 4 ). Of interest, when hypoxia is absent in tumor cells, TAMs can enhance tumor hypoxia and glycolysis ( 148 ), being both features that promote tumor aggressiveness ( 149 ).…”

Section: Impact Of Tumor Secretome In the Anti-tumor Activity Of Immune Cellsmentioning

confidence: 99%

Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner

Etxebeste-Mitxeltorena

Rincón-Loza

Martín-Antonio

2021

Front. Immunol.

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Adoptive cellular immunotherapy using chimeric antigen receptor (CAR)-modified T cells and Natural Killer (NK) cells are common immune cell sources administered to treat cancer patients. In detail, whereas CAR-T cells induce outstanding responses in a subset of hematological malignancies, responses are much more deficient in solid tumors. Moreover, NK cells have not shown remarkable results up to date. In general, immune cells present high plasticity to change their activity and phenotype depending on the stimuli they receive from molecules secreted in the tumor microenvironment (TME). Consequently, immune cells will also secrete molecules that will shape the activities of other neighboring immune and tumor cells. Specifically, NK cells can polarize to activities as diverse as angiogenic ones instead of their killer activity. In addition, tumor cell phagocytosis by macrophages, which is required to remove dying tumor cells after the attack of NK cells or CAR-T cells, can be avoided in the TME. In addition, chemotherapy or radiotherapy treatments can induce senescence in tumor cells modifying their secretome to a known as “senescence-associated secretory phenotype” (SASP) that will also impact the immune response. Whereas the SASP initially attracts immune cells to eliminate senescent tumor cells, at high numbers of senescent cells, the SASP becomes detrimental, impacting negatively in the immune response. Last, CAR-T cells are an attractive option to overcome these events. Here, we review how molecules secreted in the TME by either tumor cells or even by immune cells impact the anti-tumor activity of surrounding immune cells.

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“…In particular, tumour-associated macrophages (TAMs) are capable of being reprogrammed by tumour cells into an immunosuppressive and pro-tumourigenic phenotype, thus contributing to subdued immune responses and promoting disease progression [156]. Immune-based therapies that target macrophages in haematologic malignancies have been extensively reviewed [157]. In particular, CD47 (a surface protein that is expressed by leukaemic cells) has emerged as a key target for immunotherapy due to its role in innate immune evasion by inhibiting macrophage phagocytosis [158], with a recent review reporting current clinical trials involving the use of CD47 antagonists in haematologic malignancies [156].…”

Section: Emerging Therapies: Immunotherapies and Mitochondrial-targeted Therapiesmentioning

confidence: 99%

Therapeutic Targeting of the Leukaemia Microenvironment

Kuek

Hughes

Kotecha

et al. 2021

IJMS

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In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia.

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Targeting macrophages in cancer immunotherapy

Cited by 335 publications

References 283 publications

The methods and advances of adaptive immune receptors repertoire sequencing

The methods and advances of adaptive immune receptors repertoire sequencing

Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner

Therapeutic Targeting of the Leukaemia Microenvironment

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