Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy

Abstract

The emergence of immunotherapy has revolutionized the treatment landscape for various types of cancer. Nevertheless, lung cancer remains one of the leading causes of cancer-related mortality worldwide due to the development of resistance in most patients. As one of the most abundant groups of immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play crucial and complex roles in the development of lung cancer, including the regulation of immunosuppressive TME remodeling, metabolic reprogramming, neoangiogenesis, metastasis, and promotion of tumoral neurogenesis. Hence, relevant strategies for lung cancer therapy, such as inhibition of macrophage recruitment, TAM reprograming, depletion of TAMs, and engineering of TAMs for drug delivery, have been developed. Based on the satisfactory treatment effect of TAM-targeted therapy, recent studies also investigated its synergistic effect with current therapies for lung cancer, including immunotherapy, radiotherapy, chemotherapy, anti-epidermal growth factor receptor (anti-EGFR) treatment, or photodynamic therapy. Thus, in this article, we summarized the key mechanisms of TAMs contributing to lung cancer progression and elaborated on the novel therapeutic strategies against TAMs. We also discussed the therapeutic potential of TAM targeting as adjuvant therapy in the current treatment of lung cancer, particularly highlighting the TAM-centered strategies for improving the efficacy of anti-programmed cell death-1/programmed cell death-ligand 1 (anti-PD-1/PD-L1) treatment.

Comprehensive Analysis of Lung Adenocarcinoma and Brain Metastasis through Integrated Single-Cell Transcriptomics

“…Since the TME exerts a key influence on tumor cells and their behavior, the therapeutic approaches for modulating the TME are promising [31]. Some of the strategies that have been explored include the inhibition of macrophage recruitment, the reprogramming of tumor-associated macrophages (TAMs), the depletion of TAMs, and the engineering of TAMs [30,32,33]. Additionally, the effects of other treatment modalities, such as radiotherapy, chemotherapy, anti-EGFR treatment, or photodynamic therapy (PDT), combined with TAM-targeted therapy, have also attracted attention [33].…”

“…Some of the strategies that have been explored include the inhibition of macrophage recruitment, the reprogramming of tumor-associated macrophages (TAMs), the depletion of TAMs, and the engineering of TAMs [30,32,33]. Additionally, the effects of other treatment modalities, such as radiotherapy, chemotherapy, anti-EGFR treatment, or photodynamic therapy (PDT), combined with TAM-targeted therapy, have also attracted attention [33]. Furthermore, the targeting of other components of the TME, such as tumor-infiltrating T cells [34], cancer-associated fibroblasts [35], and the ECM [36], has been investigated as a potential therapeutic approach.…”

“…While the TME, and therapeutic strategies targeting it, have been extensively researched in lung cancer [17,33,37], the focus has predominantly been on primary tumors, leaving a notable gap in the studies related to BM. Additionally, many earlier clinical trials for immunotherapy in the context of metastatic disease have excluded patients with brain lesions due to poor survival outcomes and concerns regarding the ability of drugs to cross the blood-brain barrier (BBB) [6].…”

23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling

“…Numerous studies suggest that M2 macrophages facilitate the initiation and dissemination of tumor cells while also enhancing the tumor cells’ capacity to withstand cytotoxic chemotherapy [ 7 – 10 ]. Targeting TAMs has been demonstrated to suppress tumor progression and decrease chemoresistance [ 9 , 11 – 14 ].…”

The Triterpenoid CDDO-Methyl Ester Reduces Tumor Burden, Reprograms the Immune Microenvironment, and Protects from Chemotherapy-Induced Toxicity in a Preclinical Mouse Model of Established Lung Cancer

“…The tumor suppressive effects of NRF2 activation in immune cells in lung cancer, particularly in the myeloid lineage [ 18 , 19 ], were demonstrated. Macrophages make up a significant portion of the immune microenvironment in lung tumors, and their dynamic ability to fluctuate between anti-tumor and tumor-promoting phenotypes makes these cells an attractive target for anti-cancer therapies [ 20 ]. However, most previous studies evaluating NRF2 activation in macrophages within the lung tumor microenvironment utilized models of early-stage lung cancer, and NRF2 plays differing roles throughout carcinogenesis [ 21 ].…”