Macrophages and cancer: from mechanisms to therapeutic implications

Ostuni, Renato; Kratochvill, Franz; Murray, Peter J.; Natoli, Gioacchino

doi:10.1016/j.it.2015.02.004

Cited by 606 publications

(528 citation statements)

References 114 publications

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“…13 TAMs are local macrophages recruited to solid tumors which rather promote than suppress tumor progression. 7,14 Their infiltrate, which may be as great as half of the tumor mass, results from the so-called "cancer education" provoked by specific microenvironmental conditions. 15 These processes are reminiscent of a role of TAMs in tissue-repair in normal organs, employing neoangiogenesis, induction of trophic signals, tissue remodeling and immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

“…15 These processes are reminiscent of a role of TAMs in tissue-repair in normal organs, employing neoangiogenesis, induction of trophic signals, tissue remodeling and immunosuppression. 7 Macrophages are divided into different phenotypes such as M1/M2 and macrophages with regulatory properties. 7 TAMs skewed toward an M2-altered functional profile play a crucial role in immune evasion within tumors.…”

Section: Discussionmentioning

confidence: 99%

“…7 Macrophages are divided into different phenotypes such as M1/M2 and macrophages with regulatory properties. 7 TAMs skewed toward an M2-altered functional profile play a crucial role in immune evasion within tumors. These cells are marked by the expression of CD11b, CD14, CD33 and CD68 in humans and production of lower levels of proinflammatory cytokines, such as IL-1b, TNF-a and IL-12 but higher levels of immunosuppressive mediators, such as IL-10, TGF-b and VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that MCP-1/ CCL2 recruits cognate receptor-positive CCR2 C blood monocytes to tumors where they undergo a specific maturation pathway to TAMs by distinct tumor type-specific microenvironmental factors. 7,20 Since TAMs release a large amount of inflammatory mediators to create an corresponding environment which promotes tumor growth we screened the CTCinduced macrophage supernatants for presence of over 100 cytokines/chemokines.…”

Section: Secretory Phenotype Of Sclc Ctc-induced Macrophagesmentioning

confidence: 99%

“…6 These "tumor-educated" macrophages promote invasion, intravasation as well as survival in the circulation and durable growth at secondary lesions. 5,7 TAMs are recruited by various cytokines and chemokines, suppress the activity of cytotoxic T-lymphocytes via programmed cell death 1 ligand 1 (PD-L1) or B7-H4 and other receptors/mediators. 7,8 The mechanisms by which macrophages acquire prometastatic abilities have not been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

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Small cell lung cancer: Recruitment of macrophages by circulating tumor cells

et al. 2015

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Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 C , CD163 weak and CD68 C macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293 cell line revealed no induction of macrophages, whereas incubation of PBMNCs with recombinant CHI3L1 gave positive results. Thus, the specific contributions of CTCs in SCLC affect CFD/adipsin, possibly involved in immunity/cachexia, VDBP which gives rise to group-specific component protein-derived macrophage-activating factor (GcMAF), GDF-15/MIC-1 which enhances the malignant phenotype of tumor cells and ENA-78/CXCL5 which attracts angiogenic neutrophils. In conclusion, CTCs are competent to specifically manipulate TAMs to increase invasiveness, angiogenesis, immunosuppression and possibly lipid catabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Secretory Phenotype Of Sclc Ctc-induced Macrophagesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Small cell lung cancer: Recruitment of macrophages by circulating tumor cells

et al. 2015

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Integrated analysis of racial disparities in genomic architecture identifies a trans‐ancestry prognostic subtype in bladder cancer

et al. 2022

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The incidence of bladder cancer and patient survival vary greatly among different populations, but the influence of the associated molecular features and evolutionary processes on its clinical treatment and prognostication remains unknown. Here, we analyze the genomic architectures of 505 bladder cancer patients from Asian/Black/White populations. We identify a previously unknown association between AHNAK mutations and activity of the APOBEC‐a mutational signature, the activity of which varied substantially across populations. All significantly mutated genes but only half of arm‐level somatic copy number alterations (SCNAs) are enriched with clonal events, indicating large‐scale SCNAs as rich sources of bladder cancer clonal diversities. The prevalence of TP53 and ATM clonal mutations as well as the associated burden of SCNAs is significantly higher in Whites/Blacks than in Asians. We identify a trans‐ancestry prognostic subtype of bladder cancer characterized by enrichment of non‐muscle‐invasive patients and muscle‐invasive patients with good prognosis, increased CREBBP/FGFR3/HRAS/NFE2L2 mutations, decreased intra‐tumor heterogeneity and genome instability, and an activated tumor microenvironment.

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