The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 17(8), P. 807 - 821

Published: July 1, 2020

Abstract Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types immunotherapy, including adoptive cell transfer (ACT) immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, only subsets patients can benefit from them. Immune infiltrates in microenvironment (TME) been shown to play a key role development will affect outcomes patients. Comprehensive profiling tumor-infiltrating cells would shed light on mechanisms cancer–immune evasion, thus providing opportunities for novel therapeutic strategies. However, highly heterogeneous dynamic nature TME impedes precise dissection intratumoral cells. With recent advances single-cell technologies such as RNA sequencing (scRNA-seq) mass cytometry, systematic interrogation is feasible provide insights into functional diversities In this review, we outline progress particularly by focusing landmark studies characterization tumor-associated cells, summarize phenotypic connections with immunotherapy. We believe review could strengthen our understanding facilitate elucidation modulation progression, guide immunotherapies treatment.

Language: Английский

---

Roles of the immune system in cancer: from tumor initiation to metastatic progression

Genes & Development, Journal Year: 2018, Volume and Issue: 32(19-20), P. 1267 - 1284

Published: Oct. 1, 2018

The presence of inflammatory immune cells in human tumors raises a fundamental question oncology: How do cancer avoid the destruction by attack? In principle, tumor development can be controlled cytotoxic innate and adaptive cells; however, as develops from neoplastic tissue to clinically detectable tumors, evolve different mechanisms that mimic peripheral tolerance order tumoricidal attack. Here, we provide an update recent accomplishments, unifying concepts, future challenges study tumor-associated cells, with emphasis on metastatic carcinomas.

Language: Английский

---

Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment

Cell, Journal Year: 2018, Volume and Issue: 174(5), P. 1293 - 1308.e36

Published: June 28, 2018

Language: Английский

---

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

---

Tumor microenvironment as a therapeutic target in cancer

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 221, P. 107753 - 107753

Published: Nov. 28, 2020

Language: Английский

---

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000337 - e000337

Published: March 1, 2020

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular microenvironmental features determine the propensity of RCD drive immunity. Here, we provide updated operational definition immunogenic (ICD), discuss key factors that dictate ability dying cells response, summarize experimental assays are currently available for assessment ICD in vitro vivo, formulate guidelines their interpretation.

Language: Английский

---

Regulatory T Cells and Human Disease

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 541 - 566

Published: Feb. 4, 2020

Naturally occurring CD4+ regulatory T cells (Tregs), which specifically express the transcription factor FoxP3 in nucleus and CD25 CTLA-4 on cell surface, are a functionally distinct subpopulation actively engaged maintenance of immunological self-tolerance homeostasis. Recent studies have facilitated our understanding cellular molecular basis their generation, function, phenotypic functional stability, adaptability. It is under investigation humans how or numerical Treg anomalies, whether genetically determined environmentally induced, contribute to diseases such as autoimmune diseases. Also being addressed Tregs can be targeted control physiological pathological immune responses, for example, by depleting them enhance tumor immunity expanding treat This review discusses current immunobiology normal disease states, with perspective realization Treg-targeting therapies clinic.

Language: Английский

---

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: July 17, 2020

Abstract Regulatory T cells (Tregs) characterized by the expression of master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot field. However, Tregs are also essential for maintenance tolerance body share many molecular signalling pathways with conventional cells, including cytotoxic primary mediators tumour immunity. Hence, inability to specifically target neutralize microenvironment without globally compromising self-tolerance poses significant challenge. Here, we review recent advances characterizing tumour-infiltrating focus on functional roles costimulatory inhibitory receptors Tregs, evaluate their potential as clinical targets, systematically summarize treatment strategies. Also, propose modalities integrate our increasing knowledge phenotype function rational design checkpoint inhibitor-based combination therapies. Finally, possible strategies that can be used develop Treg-targeted

Language: Английский

---

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: May 22, 2019

The immune system and cancer have a complex relationship with the playing dual role in tumor development. effector cells of can recognize kill malignant while system-mediated inflammation also promote growth regulatory suppress anti-tumor responses. In center all responses is ability to migrate site interact each other cells. Cell adhesion molecules including receptors immunoglobulin superfamily integrins are crucial importance mediating these processes. Particularly play vital regulating aspects cell function trafficking into tissues, activation proliferation formation immunological synapse between or target both during homeostasis cancer. this review we discuss molecular mechanisms integrin microenvironment. We describe how utilize metastases could be targeted immunotherapy.

Language: Английский

---

The future of cancer immunotherapy: microenvironment-targeting combinations

Cell Research, Journal Year: 2020, Volume and Issue: 30(6), P. 507 - 519

Published: May 28, 2020

Abstract Immunotherapy holds the potential to induce durable responses, but only a minority of patients currently respond. The etiologies primary and secondary resistance immunotherapy are multifaceted, deriving not from tumor intrinsic factors, also complex interplay between cancer its microenvironment. In addressing frontiers in clinical immunotherapy, we describe two categories approaches design novel drugs combination therapies: first involves direct modification tumor, while second indirectly enhances immunogenicity through alteration By systematically factors that mediate resistance, able identify mechanistically-driven improve outcomes.

Language: Английский

---