Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Oct. 11, 2021

Abstract Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote growth, angiogenesis, invasion metastasis, along extracellular matrix (ECM) remodeling even chemoresistance. Numerous previous studies have confirmed critical role interaction between cells in tumorigenesis development. However, recently, mutual effects immune (TIME) been identified as another key factor promoting progression. The TIME mainly consists distinct populations islets is highly associated antitumor immunological state TME. interact tumor-infiltrating well other within via secretion various cytokines, growth factors, chemokines, exosomes effector molecules, consequently shaping an immunosuppressive TME that enables cancer to evade surveillance system. In-depth interactions, particularly complicated mechanisms connecting cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding direct indirect crosstalk infiltrating further summarize possible immunoinhibitory induced by In addition, present current related CAF-targeting immunotherapies briefly describe some future perspectives CAF research end.

Language: Английский

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Tumor microenvironment complexity and therapeutic implications at a glance

Cell Communication and Signaling, Journal Year: 2020, Volume and Issue: 18(1)

Published: April 7, 2020

Abstract The dynamic interactions of cancer cells with their microenvironment consisting stromal (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity cell, clonal evolution increase multidrug resistance ending in cell progression metastasis. reciprocal cell-cell/ECM interaction tumor hijacking non-malignant force lose function acquire new phenotypes that promote development invasion cells. Understanding underlying cellular molecular mechanisms governing these can be used as a novel strategy indirectly disrupt interplay contribute efficient safe therapeutic strategies fight cancer. Furthermore, tumor-derived circulating materials also diagnostic tools precisely predict monitor outcome therapy. This review evaluates such potentials various advanced models, focus on 3D systems well lab-on-chip devices.

Language: Английский

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Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 21, 2022

Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, dostarlimab) three α-PD-L1 antibodies (atezolizumab, durvalumab, avelumab) have been approved for various types of cancers. Nevertheless, low rate α-PD-1/PD-L1 therapy remains to be resolved. For most patients, PD-1/PD-L1 pathway is not sole speed-limiting factor antitumor immunity, it insufficient motivate effective by blocking axis. It has validated that some combination therapies, including plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other checkpoint agonists co-stimulatory molecule, stimulator interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, metabolic superior efficacies higher rates. Moreover, bifunctional bispecific containing moiety also elicited more potent activity. These strategies simultaneously boost multiple processes cancer-immunity cycle, remove immunosuppressive brakes, orchestrate an immunosupportive tumor microenvironment. In this review, we summarized synergistic mechanisms with therapies. focused advances α-PD-1/PD-L1-based immunomodulatory studies. Given heterogeneity across patients types, individualized selection could improve effects relieve treatment resistance.

Language: Английский

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Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(6), P. 845 - 865.e7

Published: May 20, 2021

Language: Английский

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Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 10, 2021

Abstract To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence progression because of versatile roles extracellular matrix remodeling, maintenance stemness, blood vessel formation, modulation metabolism, immune response, promotion cell proliferation, migration, invasion, therapeutic resistance. CAFs highly heterogeneous stromal cells crosstalk with is mediated by a complex intricate signaling network consisting transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers activators transcription, epidermal factor receptor, Hippo, nuclear kappa-light-chain-enhancer activated B cells, etc., pathways. These signals exhibit own special characteristics during the have potential to be targeted anticancer therapy. Therefore, comprehensive understanding these cascades interactions between necessary fully realize pivotal cancers. Herein, this review, we will summarize enormous amounts findings mediating its related targets or trials. Further, hypothesize three targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential perturbation, crosstalk-directed paving way CAF-directed host cell-directed antitumor

Language: Английский

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Combination strategies to maximize the benefits of cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Sept. 27, 2021

Abstract Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary secondary resistance to single agent immunotherapy often results treatment failure, only a minority of experience long-term benefits. This review article will discuss the relationship between response mechanisms immunotherapy. It also provide comprehensive on latest clinical status combination therapies (e.g., with chemotherapy, radiation targeted therapy), approved by US Food Drug Administration. an overview targeting cytokines other soluble immunoregulatory factors, ACT, virotherapy, innate modifiers vaccines, well that exploit alternative targets therapeutic modalities. Finally, this include stimulating insights from 2020 China Immuno-Oncology Workshop co-organized Chinese American Hematologist Oncologist Network (CAHON), National Medical Product Administration (NMPA) Tsinghua University School Medicine.

Language: Английский

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Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance

Drug Resistance Updates, Journal Year: 2020, Volume and Issue: 53, P. 100715 - 100715

Published: June 20, 2020

Language: Английский

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Immunotherapy for pancreatic cancer: A 2020 update

Cancer Treatment Reviews, Journal Year: 2020, Volume and Issue: 86, P. 102016 - 102016

Published: March 25, 2020

Language: Английский

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Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer

Cancer Discovery, Journal Year: 2021, Volume and Issue: 12(3), P. 670 - 691

Published: Oct. 12, 2021

Gastric cancer heterogeneity represents a barrier to disease management. We generated comprehensive single-cell atlas of gastric (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage exhibited cancer-associated expression profiles, individually contributing combined tumor-wide molecular collage. observed increased plasma proportions in diffuse-type tumors associated with epithelial-resident KLF2 stage-wise accrual fibroblast subpopulations marked by high INHBA FAP coexpression. Single-cell comparisons between patient-derived organoids (PDO) primary highlighted inter- intralineage similarities differences, demarcating boundaries PDOs as experimental models. complemented these findings spatial transcriptomics, orthogonal validation independent bulk RNA-sequencing cohorts, functional demonstration using vitro vivo Our results provide high-resolution resource intra- interpatient profiled malignancies at resolution feature tumors. also uncovered subtypes INHBA-FAP-high populations predictors poor prognosis. highlight potential origins deregulated the tumor ecosystem. This article is In Issue feature, p. 587.

Language: Английский

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Targeting TGFβ signal transduction for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Jan. 7, 2021

Abstract Transforming growth factor-β (TGFβ) family members are structurally and functionally related cytokines that have diverse effects on the regulation of cell fate during embryonic development in maintenance adult tissue homeostasis. Dysregulation TGFβ signaling can lead to a plethora developmental disorders diseases, including cancer, immune dysfunction, fibrosis. In this review, we focus TGFβ, well-characterized member has dichotomous role cancer progression, acting early stages as tumor suppressor late promoter. The functions not limited proliferation, differentiation, apoptosis, epithelial–mesenchymal transition, metastasis cells. Recent reports cells present microenvironment through stimulation extracellular matrix deposition, promotion angiogenesis, suppression anti-tumor reaction. pro-oncogenic roles attracted considerable attention because their intervention provides therapeutic approach for patients. However, critical function maintaining homeostasis makes targeting challenge. Here, review pleiotropic initiation summarize recent clinical advancements regarding interventions treatment, discuss remaining challenges opportunities pathway. We provide perspective synergistic therapies combine anti-TGFβ therapy with cytotoxic chemotherapy, targeted therapy, radiotherapy, or immunotherapy.

Language: Английский

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