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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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Related Experiment Video

Updated: Jun 30, 2025

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Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade.

Jie Mei1,2, Yun Cai3, Rui Xu1,2

  • 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China.

Cancer Communications (London, England)
|March 20, 2024
PubMed
Summary

This study identifies three tumor subtypes based on extracellular matrix (ECM) and immune cell activity, predicting response to immune checkpoint blockade (ICB) therapy. "Soft & hot" tumors show the best ICB response, offering new strategies for cancer treatment.

Keywords:
collagen depositionimmune infiltrationimmunotherapypan‐cancertumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Immune checkpoint blockade (ICB) has transformed cancer therapy, but predicting patient response remains a challenge.
  • The extracellular matrix (ECM) plays a critical role in modulating immune cell infiltration and anti-tumor immunity.
  • Understanding the interplay between ECM and immune microenvironment is crucial for improving ICB efficacy.

Purpose of the Study:

  • To develop an innovative classifier leveraging ECM characteristics to predict ICB therapy response.
  • To identify novel therapeutic targets based on distinct immuno-collagenic subtypes.
  • To enhance the effectiveness of ICB by stratifying patients based on tumor microenvironment features.

Main Methods:

  • Transcriptomic collagen activity and immune signatures were analyzed in 649 patients undergoing ICB therapy.
  • Three distinct immuno-collagenic subtypes were identified and validated using TCGA and in-house datasets (9,363 and 1,084 samples, respectively).
  • Preclinical models were used to investigate the mechanistic role of collagen in ICB response.

Main Results:

  • Three subtypes were defined: "soft & hot" (low collagen, high immune), "armored & cold" (high collagen, low immune), and "quiescent" (low collagen, low immune).
  • "Soft & hot" tumors demonstrated the most robust response to ICB across cancer types; collagen inhibition enhanced ICB efficacy in preclinical models.
  • B7-H3 was identified as a potential therapeutic target, highly expressed in "armored & cold" tumors associated with poor prognosis.

Conclusions:

  • Universal immuno-collagenic subtypes, identifiable via histopathology, can predict ICB responses across diverse cancers.
  • These subtypes provide insights for tailoring personalized immunotherapeutic strategies.
  • Targeting ECM-immune interactions and specific biomarkers like B7-H3 may improve ICB outcomes.