Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling

Chen, Pei-Yu; Wei, W.; Wu, Hong-Zhen; Fan, Liangsheng; Wang, Wei

doi:10.3389/fimmu.2021.671595

Cited by 46 publications

(51 citation statements)

References 98 publications

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“…Targeted CAF therapy can potentially inhibit metastasis and cancer progression by reducing immunosuppression and remodeling the tumor microenvironment. Therapeutic targeting of FAP has been described in different modalities, such as vaccines, oncolytic viruses, and nanoparticles [26]. In preclinical studies, CAF-S1 FAP+ has shown to cause resistance to anti-PD-L1 immunotherapy and reduce antitumor immunity.…”

Section: Discussionmentioning

confidence: 99%

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

et al. 2022

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Fibroblast activation protein (FAP) is highly expressed on the cancer-associated fibroblasts (CAF) of the tumor stroma. Recently, we reported the preclinical evaluation and clinical biokinetics of a novel 99mTc-labeled FAP inhibitor radioligand ([99mTc]Tc-iFAP). This research aimed to evaluate [99mTc]Tc-iFAP for the tumor stroma imaging of six different cancerous entities and analyze them from the perspective of stromal heterogeneity. [99mTc]Tc-iFAP was prepared from freeze-dried kits with a radiochemical purity of 98 ± 1%. The study included thirty-two patients diagnosed with glioma (n = 5); adrenal cortex neuroendocrine tumor (n = 1); and breast (n = 21), lung (n = 2), colorectal (n = 1) and cervical (n = 3) cancer. Patients with glioma had been evaluated with a previous cranial MRI scan and the rest of the patients had been involved in a [18F]FDG PET/CT study. All oncological diagnoses were corroborated histopathologically. The patients underwent SPECT/CT brain imaging (glioma) or thoracoabdominal imaging 1 h after [99mTc]Tc-iFAP administration (i.v., 735 ± 63 MBq). The total lesions (n = 111) were divided into three categories: primary tumors (PT), lymph node metastases (LNm), and distant metastases (Dm). [99mTc]Tc-iFAP brain imaging was positive in four high-grade WHO III–IV gliomas and negative in one treatment-naive low-grade glioma. Both [99mTc]Tc-iFAP and [18F]FDG detected 26 (100%) PT, although the number of positive LNm and Dm was significantly higher with [18F]FDG [82 (96%)], in comparison to [99mTc]Tc-iFAP imaging (35 (41%)). Peritoneal carcinomatosis lesions in a patient with recurrent colorectal cancer were only visualized with [99mTc]Tc-iFAP. In patients with breast cancer, a significant positive correlation was demonstrated among [99mTc]Tc-iFAP uptake values (Bq/cm3) of PT and the molecular subtype, being higher for subtypes HER2+ and Luminal B HER2-enriched. Four different CAF subpopulations have previously been described for LNm of breast cancer (from CAF-S1 to CAF-S4). The only subpopulation that expresses FAP is CAF-S1, which is preferentially detected in aggressive subtypes (HER2 and triple-negative), confirming that FAP+ is a marker for poor disease prognosis. The results of this pilot clinical research show that [99mTc]Tc-iFAP SPECT imaging is a promising tool in the prognostic assessment of some solid tumors, particularly breast cancer.

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Section: Discussionmentioning

confidence: 99%

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

et al. 2022

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“…As we know, cancer-associated fibroblasts exerted a strong immunomodulatory regulation, mainly suppressing the immune system and promoting tumour progression. 51,52 Thus, we deduced that CNTN1 might take a negative regulation in the tumour immune microenvironment.…”

Section: F I G U R E 8 Correlation Analysis In Different Algorithms B...mentioning

confidence: 93%

Prognostic implication and immunological value of contactin 1 expression in pan‐cancer

Zhang

Liu

et al. 2022

Clinical and Translational Dis

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“…This is a base for the formation of metastases and resistance to chemo/actinotherapy. CAF-derived exosome efficiency mainly depends on the specific miRNAs in their cargo [73,122,136,[148][149][150][151][152][153][154][155][156][157][158][159][160] (summarised in Table 4). Cancer wasting and cachexia are present in many patients in the terminal phase of malignant disease [161].…”

Section: Effect Of Cancer Cell-derived Exosomes (Caexos) On the Funct...mentioning

confidence: 99%

Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

Vokurka

Lacina

Brábek

et al. 2022

IJMS

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Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.

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Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling

Cited by 46 publications

References 98 publications

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

Prognostic implication and immunological value of contactin 1 expression in pan‐cancer

Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

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