Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs); where do they stand in tumorigenesis and how they can change the face of cancer therapy?

Tajaldini, Mahboubeh; Saeedi, Mohsen; Amiriani, Taghi; Amiriani, Amir Hossein; Sedighi, Sima; zadeh, Fatemeh Mohammad; Dehghan, Mohammad Hossien; Jahanshahi, Mehrdad; Ghandian, Maziar Zanjan; Khalili, Pedram; poorkhani, Amir houshang; Alizadeh, Ali Mohammad; Khori, Vahid

doi:10.1016/j.ejphar.2022.175087

Cited by 27 publications

(18 citation statements)

References 165 publications

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“…CAFs and TAMs are essential components of the tumor microenvironment, coordinating pro-tumor inflammation (Tajaldini et al, 2022). TAMs are the most abundant innate immune cell type in the vicinity of densely populated areas of CAF, suggesting a close relationship between TAMs and CAFs (Gunaydin, 2021).…”

Section: Interaction Between Cafs and Tumorassociated Macrophagesmentioning

confidence: 99%

“…Among the different cells present in TME, TAMs, and CAFs have been shown to operate the tissues that make up the ECM to regulate angiogenesis, tumor metastasis, and drug resistance with significant value (Monteran and Erez, 2019). It has been demonstrated that TAM and CAF in the TME establish a barrier with the ECM to isolate the action of drugs and even inhibit the killing action of immune cells, resulting in a poor prognosis and the failure of chemotherapeutic drug treatment (Tajaldini et al, 2022). Given the synergistic relationship between CAFs and TAMs in the TME in promoting cancer development, strategies to alter the polarization phenotype of TAMs should also consider the synergistic effects of CAFs, thereby contributing to a more effective antitumor immune response.…”

Section: Interaction Between Cafs and Tumorassociated Macrophagesmentioning

confidence: 99%

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CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

et al. 2023

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Cancer immunotherapy has opened a new landscape in cancer treatment, however, the poor specificity and resistance of most targeted therapeutics have limited their therapeutic efficacy. In recent years, the role of CAFs in immune regulation has been increasingly noted as more evidence has been uncovered regarding the link between cancer-associated fibroblasts (CAFs) and the evolutionary process of tumor progression. CAFs interact with immune cells to shape the tumor immune microenvironment (TIME) that favors malignant tumor progression, a crosstalk process that leads to the failure of cancer immunotherapies. In this review, we outline recent advances in the immunosuppressive function of CAFs, highlight the mechanisms of CAFs-immune cell interactions, and discuss current CAF-targeted therapeutic strategies for future study.

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Section: Interaction Between Cafs and Tumorassociated Macrophagesmentioning

confidence: 99%

Section: Interaction Between Cafs and Tumorassociated Macrophagesmentioning

confidence: 99%

CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

et al. 2023

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“…Our findings indicate that bone marrow adipocytes promoted CAF formation and suppressed CD8 + lymphocyte infiltration at the invasive front, factors that are both closely related to therapeutic resistance. [60][61][62][63][64] We therefore hypothesized that cancer cells acquire therapeutic resistance in adipo-BM after bone metastasis from the primary site. To test this, we compared cancer cell mRNA expression in bone metastasis with that in the primary site of the same case.…”

Section: Cancer Cells Acquired Drug Resistance and Immune Evasion-rel...mentioning

confidence: 99%

Bone marrow adipocytes induce cancer‐associated fibroblasts and immune evasion, enhancing invasion and drug resistance

et al. 2023

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Bone metastasis occurs frequently in cancer patients. Conventional therapies have limited therapeutic outcomes, and thus, exploring the mechanisms of cancer progression in bone metastasis is important to develop new effective therapies. In the bone microenvironment, adipocytes are the major stromal cells that interact with cancer cells during bone metastasis. However, the comprehensive functions of bone marrow adipocytes in cancer progression are not yet fully understood. To address this, we investigated the role of bone marrow adipocytes on cancer cells, by focusing on an invasive front that reflects the direct effects of stromal cells on cancer. In comprehensive histopathological and genetic analysis using bone metastasis specimens, we examined invasive fronts in bone metastasis and compared invasive fronts with adipocyte-rich bone marrow (adipo-BM) to those with hematopoietic cell-rich bone marrow (hemato-BM) as a normal counterpart of adipocytes. We found morphological complexity of the invasive front with adipo-BM was significantly higher than that with hemato-BM. Based on immunohistochemistry, the invasive front with adipo-BM comparatively had a significantly increased cancer-associated fibroblast (CAF) markerpositive area and lower density of CD8 + lymphocytes compared to that with hemato-BM. RNA sequencing analysis of primary and bone metastasis cancer revealed that bone metastasized cancer cells acquired drug resistance-related gene expression phenotypes. Clearly, these findings indicate that bone marrow adipocytes provide a favorable tumor microenvironment for cancer invasion and therapeutic resistance of bone metastasized cancers through CAF induction and immune evasion, providing a potential target for the treatment of bone metastasis.

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“…The inhibition of the NF-κB pathway by the siRNA pathway could transform TAM into M1 macrophages ( Ortega et al, 2016 ). Other molecules also impact the polarization of TAMs, such as HDAC, and the microRNA processing enzyme DICER, because blocking HDAC or DICER could produce M1 phenotypes ( Tie et al, 2022a ; Tajaldini et al, 2022 ). Third, restoring phagocytic capacity is crucial for TAMs.…”

Section: Effector Phasementioning

confidence: 99%

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Wang

Zhuling³

et al. 2022

Front. Genet.

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In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

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Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs); where do they stand in tumorigenesis and how they can change the face of cancer therapy?

Cited by 27 publications

References 165 publications

CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

Bone marrow adipocytes induce cancer‐associated fibroblasts and immune evasion, enhancing invasion and drug resistance

The soldiers needed to be awakened: Tumor-infiltrating immune cells

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