Targeting macrophages: a novel treatment strategy in solid tumors

Abstract

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.

Evaluation of CD47 in the Suppressive Tumor Microenvironment and Immunotherapy in Prostate Cancer

“…Based on the sonodynamic therapy and the characteristics of macrophage apoptosis induced by zoledronic acid, Cao et al [ 43 ] constructed M2-like TAMs targeted nanoliposomes by using M2-pep, a polypeptide sequence that tends to bind M2-like TAMs, which effectively consumed M2-like TAMs, alleviated tumor hypoxia, increased the release of immune-promoting factors, and achieved antitumor effects. Increasing evidence shows that TME can change the properties of macrophages to maintain dynamic tissue homeostasis, and targeting tam has become a promising immunotherapy strategy in the field of solid tumors [ 44 , 45 ]. Given the plasticity of macrophages, macrophages at different locations within the same tumor may receive different signals from their immediate microenvironment and develop different functions [ 46 ].…”

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

“…Because CD47 is ubiquitously expressed throughout the body, the lack of tumor selectivity leads to undesirable side effects such as anemia and thrombocytopenia [34]. Attempts to overcome this limitation have included the development of bispecific antibodies, such as TG-1801 and IMM0306, that target both CD47 and tumor cells, thereby aiming to restrict activity against non-tumor cells [35][36][37]. Nevertheless, these therapeutic approaches suffer from a lower affinity for CD47, thus diminishing drug efficacy.…”

The role of tumor-associated macrophages in tumor immune evasion

“…According to prevailing research, M1 macrophages are generally recognized as initiators of the healing process, whereas M2 macrophages are considered to facilitate the resolution of healing (Spiller and Koh 2017 ). In cases where the wound healing process is prolonged or does not correctly conclude, a pathological form of fibrosis, driven by Th2 responses and mediated by M2 macrophages, is commonly believed to occur (Wynn and Barron 2010 ).M2 macrophages promote tissue remodeling and angiogenesis within the TME, contributing to tumor progression ( Liu et al 2022 ). They can remodel the TME through interactions with other cells, impacting their number, activity, and phenotype associated with drug resistance (Wang, et al 2021 ).…”