Biology and therapeutic targeting of tumour‐associated macrophages

Beltraminelli, Tim; Palma, Michele De

doi:10.1002/path.5403

Cited by 70 publications

(51 citation statements)

References 307 publications

(544 reference statements)

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“…Three CSF1R-blocking mAb, RG7155 (emactuzumab), IMC-CS4 and FPA008 are in clinical evaluation, alone or in combination therapy, in several solid tumors [29,30]. In mice models of breast cancer and melanoma, CSF1R-blocking antibodies were not able to arrest the growth of the primary tumors but significantly reduced the development of metastases [31]. Only a partial response was observed for emactuzumab in combination with paclitaxel for the treatment of advanced solid tumors, even if M2 TAM depletion and repolarization toward M1 was obtained [32].…”

Section: Strategies Aimed At Tam Depletionmentioning

confidence: 99%

Tumor-Associated Macrophage Status in Cancer Treatment

Malfitano

Pisanti

Napolitano

et al. 2020

Cancers

123

105

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Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors. TAMs, exhibiting anti-inflammatory phenotype, are key players in cancer progression, metastasis and resistance to therapy. A high TAM infiltration is generally associated with poor prognosis, but macrophages are highly plastic cells that can adopt either proinflammatory/antitumor or anti-inflammatory/protumor features in response to tumor microenvironment stimuli. In the context of cancer therapy, many anticancer therapeutics, apart from their direct effect on tumor cells, display different effects on TAM activation status and density. In this review, we aim to evaluate the indirect effects of anticancer therapies in the modulation of TAM phenotypes and pro/antitumor activity.

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Section: Strategies Aimed At Tam Depletionmentioning

confidence: 99%

Tumor-Associated Macrophage Status in Cancer Treatment

Malfitano

Pisanti

Napolitano

et al. 2020

Cancers

123

105

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“…We did not find a statistically significant correlation between the percentage of MO/MA with PD-L1 or PD-L2 expression and the clinical parameters of the patients. In turn, studies conducted by other authors and preliminary clinical trials indicate that TAMs are highly involved in the early-stage spread of OC [ 54 , 55 ]. The data obtained by Silverberg [ 5 ] show that PD-L1 expression on monocytes and CD14 + cells in PB was significantly higher at the early stage (FIGO I) of OC in comparison to benign tumors.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer

Wertel

Suszczyk

Pawłowska

et al. 2020

Journal of Immunology Research

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Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n=78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p<0.0001). Significantly higher (p<0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n=31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.

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“…Tumor metastasis is one of the important signs to determine the stages of tumor. Ectopic tumor formation is caused by tumor cell metastasis through blood vessels and lymphatic vessels [56]. These all pose huge challenges for tumor treatment, making it difficult to cure and easy to relapse.…”

Section: Tams and Tumor Proliferation Invasion And Metastasismentioning

confidence: 99%

Tumor-associated macrophages: role in tumorigenesis and immunotherapy implications

Zhu¹,

羅²,

Li³

et al. 2021

J. Cancer

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Tumor-associated macrophages (TAMs) occupy an important position in the tumor microenvironment (TME), they are a highly plastic heterogeneous population with complex effects on tumorigenesis and development. TAMs secrete a variety of cytokines, chemokines, and proteases, which promote the remodeling of extracellular matrix, tumor cell growth and metastasis, tumor vessel and lymphangiogenesis, and immunosuppression. TAMs with different phenotypes have different effects on tumor proliferation and metastasis. TAMs act a pivotal part in occurrence and development of tumors, and are very attractive target to inhibit tumor growth and metastasis in tumor immunotherapy. This article reviews the interrelationship between TAMs and tumor microenvironment and its related applications in tumor therapy.

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Biology and therapeutic targeting of tumour‐associated macrophages

Cited by 70 publications

References 307 publications

Tumor-Associated Macrophage Status in Cancer Treatment

Tumor-Associated Macrophage Status in Cancer Treatment

Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer

Tumor-associated macrophages: role in tumorigenesis and immunotherapy implications

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Biology and therapeutic targeting of tumour‐associated macrophages

Cited by 70 publications

References 307 publications

Tumor-Associated Macrophage Status in Cancer Treatment

Tumor-Associated Macrophage Status in Cancer Treatment

Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer

Tumor-associated macrophages: role in tumorigenesis and immunotherapy implications

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Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer