The Emerging Roles of Pericytes in Modulating Tumor Microenvironment

Sun, Ruipu; Kong, Xiangbin; Qiu, Xiaoyi; Huang, Cheng; Wong, Ping-Pui

doi:10.3389/fcell.2021.676342

Cited by 48 publications

(52 citation statements)

References 122 publications

(80 reference statements)

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“…However, Iba-1 immunopositive cell debris were hardly observed around tumor cell areas after the Fuco-WT PC IV therapy ( Figure 4A and Supplementary Figures S5A,B ). Interestingly, the macrophage activation marker CD68, also expressed in some cases in activated PC and microglia ( Navarro et al, 2016 ; Shibahara et al, 2020 ; Sun et al, 2021 ), was highly expressed just in grafts of the mice treated with the KO PC intracranial therapy ( Figure 4B and Supplementary Figure S5C ).…”

Section: Resultsmentioning

confidence: 99%

Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression

Molina

García‐Bernal

Salinas

et al. 2022

Front. Cell Dev. Biol.

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Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment.Methods: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared.Results: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination.Conclusion: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression.

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Section: Resultsmentioning

confidence: 99%

Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression

Molina

García‐Bernal

Salinas

et al. 2022

Front. Cell Dev. Biol.

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“…Interestingly, pericytes not only have a role in maintaining blood vessels' integrity but also are multipotent cells, serving as a source of stem cells in tumors [80]. They also display tumor proliferative and immunomodulatory effects via the secretion of chemokines and cytokines [81].…”

Section: Stromal Cells In the Tmementioning

confidence: 99%

Cytokine-Induced Senescence in the Tumor Microenvironment and Its Effects on Anti-Tumor Immune Responses

Rentschler

Braumüller

Briquez

et al. 2022

Cancers

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In contrast to surgical excision, chemotherapy or radiation therapy, immune checkpoint blockade therapies primarily influence cells in the tumor microenvironment, especially the tumor-associated lymphocytes and antigen-presenting cells. Besides complete remission of tumor lesions, in some patients, early tumor regression is followed by a consolidation phase where residing tumors remain dormant. Whereas the cytotoxic mechanisms of the regression phase (i.e., apoptosis, necrosis, necroptosis, and immune cell-mediated cell death) have been extensively described, the mechanisms underlying the dormant state are still a matter of debate. Here, we propose immune-mediated induction of senescence in cancers as one important player. Senescence can be achieved by tumor-associated antigen-specific T helper 1 cells, cytokines or antibodies targeting immune checkpoints. This concept differs from cytotoxic treatment, which often targets the genetic makeup of cancer cells. The immune system’s ability to establish “defensive walls” around tumors also places the tumor microenvironment into the fight against cancer. Those “defensive walls” isolate the tumor cells instead of increasing the selective pressure. They also keep the tumor cells in a non-proliferating state, thereby correcting the derailed tissue homeostasis. In conclusion, strengthening the senescence surveillance of tumors by the immune cells of the microenvironment is a future goal to dampen this life-threatening disease.

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“…CAFs' co-culture use is required to induce tumor plasticity in 3D models [53,54]. Pericytes interact with TME elements through the production of chemokines and cytokines, but may also polarize into CAFs within stimulation of tumor fibrosis [55]. Pericytes take an important role in tumor progression through the formation of tumor stroma, immune cells regulation, tumor angiogenesis, and neovascularization development and engagement into defeating the brain-blood barrier through lung cancer brain metastasis formation.…”

Section: Tumor Stromamentioning

confidence: 99%

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Wieleba

Wojas‐Krawczyk

Krawczyk

et al. 2022

IJMS

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Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor–tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

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The Emerging Roles of Pericytes in Modulating Tumor Microenvironment

Cited by 48 publications

References 122 publications

Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression

Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression

Cytokine-Induced Senescence in the Tumor Microenvironment and Its Effects on Anti-Tumor Immune Responses

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

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