Tumor-associated macrophages: role in tumorigenesis and immunotherapy implications

Zhu, Shunyao; 羅, 志偉; Li, Xixi; Han, Xiao‐Jian; Zhang, Ting

doi:10.7150/jca.49692

Cited by 52 publications

(39 citation statements)

References 117 publications

(119 reference statements)

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“…In contrast, M2 macrophages tune inflammation and adaptive immunity by down-regulating MHC class II and IL-12 expression and upregulating IL-10, scavenger receptor A, and arginase [43,45,46]. Most TAMs are associated with M2 macrophages in promoting tumor angiogenesis and tissue remodeling [47][48][49]. TAM infiltration is correlated with PCa Gleason scores and serum PSA levels in PCa patients and is associated with increased recurrence rates and poor prognosis [50][51][52][53].…”

Section: Inflammatory Signaling and Myeloid Cellsmentioning

confidence: 99%

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Zhong

Huang

Chen

et al. 2021

JCM

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Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.

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Section: Inflammatory Signaling and Myeloid Cellsmentioning

confidence: 99%

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Zhong

Huang

Chen

et al. 2021

JCM

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“…Such interactions often confer a survival advantage for cancer cells and resistance to anticancer therapy. Macrophages recruited into TME, termed tumor-associated macrophages (TAMs), represent the major innate immune component of the stroma and play important roles in tumor development and progression as well as intratumoral immune status [ 4 , 5 , 6 ]. There has been a growing body of evidence supporting that high density of TAMs is associated with poor prognosis, drug resistance, enhanced angiogenesis, and metastasis in cancer [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Reprograming of Tumor-Associated Macrophages in Breast Tumor-Bearing Mice under Chemotherapy by Targeting Heme Oxygenase-1

Kim

Park

et al. 2021

Antioxidants

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Tumor-associated macrophages (TAMs) represent one of the most abundant components of the tumor microenvironment and play important roles in tumor development and progression. TAMs display plasticity and functional heterogeneity as reflected by distinct phenotypic subsets. TAMs with an M1 phenotype have proinflammatory and anti-tumoral properties whereas M2-like TAMs exert anti-inflammatory and pro-tumoral functions. Tumor cell debris generated during chemotherapy can stimulate primary tumor growth and recurrence. According to our previous study, phagocytic engulfment of breast tumor cell debris by TAMs attenuated chemotherapeutic efficacy through the upregulation of heme oxygenase-1 (HO-1). To verify the impact of HO-1 upregulation on the profile of macrophage polarization during cytotoxic therapy, we utilized a syngeneic murine breast cancer (4T1) model in which tumor bearing mice were treated with paclitaxel (PTX). PTX treatment markedly downregulated the surface expression of the M1 marker CD86 in infiltrated TAMs. Notably, there were significantly more cytotoxic CD8+ T cells in tumors of mice treated with PTX plus the HO-1 inhibitor, zinc protophorphyrin IX (ZnPP) than in mice treated with PTX alone. Interestingly, the tumor-inhibiting efficacy of PTX and ZnPP co-treatment was abrogated when macrophages were depleted by clodronate liposomes. Macrophage depletion also decreased the intratumoral CD8+ T cell population and downregulated the expression of Cxcl9 and Cxcl10. The expression of the M1 phenotype marker, CD86 was higher in mice injected with PTX plus ZnPP than that in mice treated with PTX alone. Conversely, the PTX-induced upregulation of the M2 marker gene, Il10 in CD11b+ myeloid cells from 4T1 tumor-bearing mice treated was dramatically reduced by the administration of the HO-1 inhibitor. Genetic ablation of HO-1 abolished the inhibitory effect of 4T1 tumor cell debris on expression of M1 marker genes, Tnf and Il12b, in LPS-stimulated BMDMs. HO-1-deficient BMDMs exposed to tumor cell debris also exhibited a diminished expression of the M2 macrophage marker, CD206. These findings, taken all together, provide strong evidence that HO-1 plays a pivotal role in the transition of tumor-inhibiting M1-like TAMs to tumor-promoting M2-like ones during chemotherapy.

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“…Reprogramming macrophages from M2 to M1 polarization can be achieved through various means, such as by using IL-12, CD40 agonists, or CSF-1R inhibitors (209)(210)(211). In addition, "don't eat me" molecules, such as CD47 and MHC-I, on tumor cells inhibit the phagocytic function of macrophages by binding SIRPa or LILRB1, respectively, on macrophages (64,212).…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

et al. 2022

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Macrophages play critical roles in tumor progression. In the tumor microenvironment, macrophages display highly diverse phenotypes and may perform antitumorigenic or protumorigenic functions in a context-dependent manner. Recent studies have shown that macrophages can be engineered to transport drug nanoparticles (NPs) to tumor sites in a targeted manner, thereby exerting significant anticancer effects. In addition, macrophages engineered to express chimeric antigen receptors (CARs) were shown to actively migrate to tumor sites and eliminate tumor cells through phagocytosis. Importantly, after reaching tumor sites, these engineered macrophages can significantly change the otherwise immune-suppressive tumor microenvironment and thereby enhance T cell-mediated anticancer immune responses. In this review, we first introduce the multifaceted activities of macrophages and the principles of nanotechnology in cancer therapy and then elaborate on macrophage engineering via nanotechnology or genetic approaches and discuss the effects, mechanisms, and limitations of such engineered macrophages, with a focus on using live macrophages as carriers to actively deliver NP drugs to tumor sites. Several new directions in macrophage engineering are reviewed, such as transporting NP drugs through macrophage cell membranes or extracellular vesicles, reprogramming tumor-associated macrophages (TAMs) by nanotechnology, and engineering macrophages with CARs. Finally, we discuss the possibility of combining engineered macrophages and other treatments to improve outcomes in cancer therapy.

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Tumor-associated macrophages: role in tumorigenesis and immunotherapy implications

Cited by 52 publications

References 117 publications

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Reprograming of Tumor-Associated Macrophages in Breast Tumor-Bearing Mice under Chemotherapy by Targeting Heme Oxygenase-1

Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

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