Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects

Cheng, Daoan; Ge, Kele; Xue, Yan; Wang, Banglu; Chen, Rui; Zhao, Weiqing; Fang, Cheng; Ji, Mei

doi:10.3389/fimmu.2023.1209947

Cited by 9 publications

(3 citation statements)

References 140 publications

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“…It was demonstrated that treatment with osimertinib could promote the formation and release of wild type EGFR (wtEGFR)-harbouring exosomes in wtEGFR-expressing NSCLC cells by upregulating a Rab GTPase (RAB17), and exosome-mediated intercellular transfer of wtEGFR further triggered osimertinib resistance in mutEGFR NSCLC through activating downstream PI3K/AKT and MAPK signaling pathways [ 383 ]. In addition, exosomes derived from M2 type TAMs were also showed to confer osimertinib resistance in NSCLC through MSTRG.292666.16‑miR‑6836‑5p‑MAPK8IP3 axis, suggesting that targeting TAMs may help to circumvent resistance of EGFR-TKIs [ 384 , 385 ]. The monoclonal antibody trastuzumab is the first HER2-targeted drug approved for the treatment of patients with HER2-positive breast cancer [ 386 ].…”

Section: Tumor Biology Of Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Wu,

Cao,

Chen

et al. 2024

Biol Proced Online

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Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. Exosomes can be derived from cancer cells as well as cellular components in tumor microenvironment. After secretion, the exosomes carrying a wide range of bioactive cargos can be ingested by local or distant recipient cells. The released cargos act through a variety of mechanisms to elicit multiple biological effects and impact most if not all hallmarks of cancer. Moreover, owing to their excellent biocompatibility and capability of being easily engineered or modified, exosomes are currently exploited as a promising platform for cancer targeted therapy. In this review, we first summarize the current knowledge of roles of exosomes in risk and etiology, initiation and progression of cancer, as well as their underlying molecular mechanisms. The aptamer-modified exosome as a promising platform for cancer targeted therapy is then briefly introduced. We also discuss the future directions for emerging roles of exosome in tumor biology and perspective of aptamer-modified exosomes in cancer therapy.

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Section: Tumor Biology Of Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Wu,

Cao,

Chen

et al. 2024

Biol Proced Online

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“…Data supporting anti-CD47 as an active therapy combined with the potential of small-molecule therapies to modify macrophage polarity supported development of a platform that would identify combination therapies that could increase (or decrease) the activity of anti-CD47 in NSCLC. This strategy could have clinical relevance, as TAMs, likely M2 like, have been shown to drive resistance to EGFR inhibitors in NSCLC ( 14 ). Vaccaro and colleagues implemented an innovative drug screening platform to find therapies that have the ability to increase cancer cell susceptibility to macrophage-induced destruction ( 15 ).…”

Section: Exploiting Phenotypic Plasticity Of Macrophagesmentioning

confidence: 99%

Enhancing anticancer activity of macrophages through rational drug combinations

Mills,

Labrie

2024

Journal of Clinical Investigation

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Targeting tumor-associated macrophages (TAMs) is an emerging approach being tested in multiple clinical trials. TAMs, depending on their differentiation state, can exhibit pro- or antitumorigenic functions. For example, the M2-like phenotype represents a protumoral state that can stimulate tumor growth, angiogenesis, metastasis, therapy resistance, and immune evasion by expressing immune checkpoint proteins. In this issue of the JCI , Vaccaro and colleagues utilized an innovative drug screen approach to demonstrate that targeting driver oncogenic signaling pathways concurrently with anti-CD47 sensitizes tumor cells, causing them to undergo macrophage-induced phagocytosis. The combination treatment altered expression of molecules on the tumor cells that typically limit phagocytosis. It also reprogrammed macrophages to an M1-like antitumor state. Moreover, the approach was generalizable to tumor cells with different oncogenic pathways, opening the door to precision oncology–based rationale combination therapies that have the potential to improve outcomes for patients with oncogene-driven lung cancers and likely other cancer types.

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“…Among these, tumor-associated macrophages (TAMs) are the most abundant (15,16). Macrophages in the normal body have valued biological functions, including processing and presenting antigens, regulating immunity, resisting microorganisms, clearing foreign bodies, phagocytosis, and tissue remodeling (17)(18)(19)(20). In specific microenvironments, macrophages polarize into subtypes with various biological capabilities, i.e., M1-type macrophages and M2-type macrophages (21-23).…”

Section: Introductionmentioning

confidence: 99%

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Qiu,

Lu,

et al. 2024

Front. Immunol.

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Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of the gastric mucosa. The pathogenesis of GC is intricately linked to the tumor microenvironment within which the cancer cells reside. Tumor-associated macrophages (TAMs) primarily differentiate from peripheral blood monocytes and can be broadly categorized into M1 and M2 subtypes. M2-type TAMs have been shown to promote tumor growth, tissue remodeling, and angiogenesis. Furthermore, they can actively suppress acquired immunity, leading to a poorer prognosis and reduced tolerance to chemotherapy. Exosomes, which contain a myriad of biologically active molecules including lipids, proteins, mRNA, and noncoding RNAs, have emerged as key mediators of communication between tumor cells and TAMs. The exchange of these molecules via exosomes can markedly influence the tumor microenvironment and consequently impact tumor progression. Recent studies have elucidated a correlation between TAMs and various clinicopathological parameters of GC, such as tumor size, differentiation, infiltration depth, lymph node metastasis, and TNM staging, highlighting the pivotal role of TAMs in GC development and metastasis. In this review, we aim to comprehensively examine the bidirectional communication between GC cells and TAMs, the implications of alterations in the tumor microenvironment on immune escape, invasion, and metastasis in GC, targeted therapeutic approaches for GC, and the efficacy of potential GC drug resistance strategies.

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Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects

Cited by 9 publications

References 140 publications

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Enhancing anticancer activity of macrophages through rational drug combinations

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

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