MaltSci 麦伴科研

Appearance

Curated Papers > High-impact authoritative literature on "tumor microenvironment"

Innate and adaptive immune cells in the tumor microenvironment. ​

Literature Information ​

DOI10.1038/ni.2703
PMID24048123
JournalNature immunology
Impact Factor27.6
JCR QuartileQ1
Publication Year2013
Times Cited2295
Keywordstumor microenvironment, immune cells, T cells, immune evasion, immunotherapy
Literature TypeJournal Article, Review
ISSN1529-2908
Pages1014-22
Issue14(10)
AuthorsThomas F Gajewski, Hans Schreiber, Yang-Xin Fu

TL;DR ​

This study identifies two distinct phenotypes of tumor microenvironments that enable cancer cells to evade immune recognition by CD8(+) T cells: one characterized by T cell inflammation and immune suppressive pathways, and another lacking T cell infiltration that relies on immune exclusion or ignorance. Understanding these phenotypes is crucial for developing targeted immunotherapeutic strategies to enhance treatment efficacy against different tumor types.

Search for more papers on MaltSci.com ​

tumor microenvironment · immune cells · T cells · immune evasion · immunotherapy

Abstract ​

Most tumor cells express antigens that can mediate recognition by host CD8(+) T cells. Cancers that are detected clinically must have evaded antitumor immune responses to grow progressively. Recent work has suggested two broad categories of tumor escape based on cellular and molecular characteristics of the tumor microenvironment. One major subset shows a T cell-inflamed phenotype consisting of infiltrating T cells, a broad chemokine profile and a type I interferon signature indicative of innate immune activation. These tumors appear to resist immune attack through the dominant inhibitory effects of immune system-suppressive pathways. The other major phenotype lacks this T cell-inflamed phenotype and appears to resist immune attack through immune system exclusion or ignorance. These two major phenotypes of tumor microenvironment may require distinct immunotherapeutic interventions for maximal therapeutic effect.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. How do the interactions between innate and adaptive immune cells influence the efficacy of immunotherapy in different tumor microenvironments?
  2. What specific molecular pathways are involved in the immune suppression observed in T cell-inflamed versus non-inflamed tumor phenotypes?
  3. How can understanding the chemokine profiles in the tumor microenvironment aid in the development of targeted immunotherapies?
  4. What role does the type I interferon signature play in shaping the adaptive immune response within the tumor microenvironment?
  5. How might future research on immune cell plasticity in tumors inform the design of combination therapies for cancer treatment?

Key Findings ​

Research Background and Purpose ​

The review article discusses the role of tissue-resident leukocytes, specifically innate and adaptive immune cells, in the tumor microenvironment. It highlights how tumors evade immune detection and how understanding these mechanisms can lead to more effective immunotherapies.

Main Methods/Materials/Experimental Design ​

The authors employed a combination of human tissue analyses and mechanistic studies using mouse models to explore the immune landscape of tumors. They classified tumors into two major phenotypes based on their immune microenvironment: T cell-inflamed and non-T cell-inflamed tumors.

Mermaid diagram

Key Results and Findings ​

  1. Tumor Phenotypes: Two main tumor microenvironment phenotypes were identified:

    • T Cell-Inflamed: Characterized by the presence of CD8+ T cells, chemokines (e.g., CXCL9, CXCL10), and a type I interferon signature. These tumors are often resistant to immune attack due to inhibitory pathways like PD-L1 and IDO.
    • Non-T Cell-Inflamed: These tumors lack T cell infiltration and show minimal immune suppression, suggesting a different mechanism of immune evasion.

  2. Prognostic Value: The presence of CD8+ T cells in tumors correlates with better clinical outcomes across various cancer types, indicating the potential of the 'immunoscore' as a biomarker for patient prognosis.

  3. Mechanisms of Immune Evasion: Tumors utilize various strategies to evade immune detection, including:

    • Upregulation of inhibitory pathways (e.g., PD-L1, IDO).
    • Induction of immunosuppressive myeloid cells and regulatory T cells (Tregs).
    • Altered chemokine expression affecting T cell recruitment.

Main Conclusions/Significance/Innovation ​

The study emphasizes the importance of understanding the tumor microenvironment's immune landscape for developing targeted immunotherapies. The differentiation between T cell-inflamed and non-T cell-inflamed tumors suggests that tailored therapeutic strategies are necessary. The findings support the idea that specific immunosuppressive pathways can be targeted to enhance antitumor immunity.

Research Limitations and Future Directions ​

  • Limitations: The review primarily focuses on certain cancer types, and the findings may not be universally applicable across all tumors. Additionally, the complexity of the tumor microenvironment and interpatient variability complicate the translation of these findings into clinical practice.

  • Future Directions: Further research is needed to explore:

    • The role of the microbiome in shaping immune responses in the tumor microenvironment.
    • The development of combination therapies that address both immune suppression and promote T cell infiltration.
    • The identification of additional biomarkers to predict responses to immunotherapy across diverse cancer types.

This comprehensive understanding of the immune landscape in tumors will be crucial for the advancement of effective cancer immunotherapies.

References ​

  1. Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell cytotoxicity by enabling missing-self recognition. - Jason H Fine;Peter Chen;Aruz Mesci;David S J Allan;Stephan Gasser;David H Raulet;James R Carlyle - Cancer research (2010)
  2. Mechanisms of the antitumor activity of human Vγ9Vδ2 T cells in combination with zoledronic acid in a preclinical model of neuroblastoma. - Emma Di Carlo;Paola Bocca;Laura Emionite;Michele Cilli;Giuseppe Cipollone;Fabio Morandi;Lizzia Raffaghello;Vito Pistoia;Ignazia Prigione - Molecular therapy : the journal of the American Society of Gene Therapy (2013)
  3. GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development. - Vincent G Brichard;Diane Lejeune - Vaccine (2007)
  4. Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. - Guilian Niu;Tammy Bowman;Mei Huang;Steve Shivers;Douglas Reintgen;Adil Daud;Alfred Chang;Alan Kraker;Richard Jove;Hua Yu - Oncogene (2002)
  5. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. - L Chen;S Ashe;W A Brady;I Hellström;K E Hellström;J A Ledbetter;P McGowan;P S Linsley - Cell (1992)
  6. Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer. - Kalyani Narra;Stefanie R Mullins;Hyung-Ok Lee;Brenda Strzemkowski-Brun;Kimberly Magalong;Victoria J Christiansen;Patrick A McKee;Brian Egleston;Steven J Cohen;Louis M Weiner;Neal J Meropol;Jonathan D Cheng - Cancer biology & therapy (2007)
  7. Densely granulated murine NK cells eradicate large solid tumors. - Rebecca B Liu;Boris Engels;Ainhoa Arina;Karin Schreiber;Elizabeth Hyjek;Andrea Schietinger;David C Binder;Eric Butz;Thomas Krausz;Donald A Rowley;Bana Jabri;Hans Schreiber - Cancer research (2012)
  8. Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases. - Ping Yu;Youjin Lee;Yang Wang;Xiaojuan Liu;Sogyong Auh;Thomas F Gajewski;Hans Schreiber;Zhaoyang You;Campbell Kaynor;Xinzhong Wang;Yang-Xin Fu - Journal of immunology (Baltimore, Md. : 1950) (2007)
  9. Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. - Shuang Wei;Ilona Kryczek;Linhua Zou;Ben Daniel;Pui Cheng;Peter Mottram;Tyler Curiel;Andrzej Lange;Weiping Zou - Cancer research (2005)
  10. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. - Luca Gattinoni;Steven E Finkelstein;Christopher A Klebanoff;Paul A Antony;Douglas C Palmer;Paul J Spiess;Leroy N Hwang;Zhiya Yu;Claudia Wrzesinski;David M Heimann;Charles D Surh;Steven A Rosenberg;Nicholas P Restifo - The Journal of experimental medicine (2005)

Literatures Citing This Work ​

  1. Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. - Fahed Hakim;Yang Wang;Shelley X L Zhang;Jiamao Zheng;Esma S Yolcu;Alba Carreras;Abdelnaby Khalyfa;Haval Shirwan;Isaac Almendros;David Gozal - Cancer research (2014)
  2. Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. - Isaac Almendros;Yang Wang;Lev Becker;Frances E Lennon;Jiamao Zheng;Brittney R Coats;Kelly S Schoenfelt;Alba Carreras;Fahed Hakim;Shelley X Zhang;Ramon Farré;David Gozal - American journal of respiratory and critical care medicine (2014)
  3. New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. - Deepak Mittal;Matthew M Gubin;Robert D Schreiber;Mark J Smyth - Current opinion in immunology (2014)
  4. Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer patients. - Wen-Chao Wu;Hong-Wei Sun;Hai-Tian Chen;Jing Liang;Xing-Juan Yu;Chong Wu;Zilian Wang;Limin Zheng - Proceedings of the National Academy of Sciences of the United States of America (2014)
  5. The two faces of IL-6 in the tumor microenvironment. - Daniel T Fisher;Michelle M Appenheimer;Sharon S Evans - Seminars in immunology (2014)
  6. A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. - Shoichi Hazama;Yusuke Nakamura;Hiroko Takenouchi;Nobuaki Suzuki;Ryouichi Tsunedomi;Yuka Inoue;Yoshihiro Tokuhisa;Norio Iizuka;Shigefumi Yoshino;Kazuyoshi Takeda;Hirokazu Shinozaki;Akira Kamiya;Hiroyuki Furukawa;Masaaki Oka - Journal of translational medicine (2014)
  7. Emerging immunologic biomarkers: setting the (TNM-immune) stage. - Janis M Taube - Clinical cancer research : an official journal of the American Association for Cancer Research (2014)
  8. Role of Exosomes Released by Dendritic Cells and/or by Tumor Targets: Regulation of NK Cell Plasticity. - Katrin S Reiners;Juliane Dassler;Christoph Coch;Elke Pogge von Strandmann - Frontiers in immunology (2014)
  9. Immune response and the tumor microenvironment: how they communicate to regulate gastric cancer. - Keunwook Lee;Hyekyung Hwang;Ki Taek Nam - Gut and liver (2014)
  10. Heterogeneity in immune responses: from populations to single cells. - Rahul Satija;Alex K Shalek - Trends in immunology (2014)

... (2285 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology