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Cited by 10Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyGene expression and cancer classification

A Computational Approach Identifies Immunogenic Features of Prognosis in Human Cancers

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Manoharan, Malini, Mandloi, Nitin, Priyadarshini, Sushri, Patil, Ashwini, Gupta, Rohit, Iyer, Laxman, Gupta, Ravi, Chaudhuri, Amitabha·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.03017PMC PMC6308325
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Abstract

A large number of tumor intrinsic and extrinsic factors determine long-term survival in human cancers. In this study, we stratified 9120 tumors from 33 cancers with respect to their immune cell content and identified immunogenomic features associated with long-term survival. Our analysis demonstrates that tumors infiltrated by CD8+ T cells expressing higher levels of activation marker (PD1hi) along with TCR signaling genes and cytolytic T cell markers (IL2hi/TNF-αhi/IFN-γhi/GZMA-Bhi) extend survival, whereas survival benefit was absent for tumors infiltrated by anergic and hyperexhausted CD8+ T cells characterized by high expression of CTLA-4, TIM3, LAG3 and genes linked to PI3K signaling pathway. The computational approach of using robust and highly specific gene expression signatures to deconvolute the tumor microenvironment has important clinical applications, such as selecting patients who will benefit from checkpoint inhibitor treatment.

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  • In the tumor microenvironment, efferocytosis promotes an immunosuppressive environment by polarizing tumor-associated macrophages toward a tumor-promoting M2 phenotype.

    “While it helps clear apoptotic tumor cells, it also promotes an immunosuppressive environment by polarizing tumor-associated macrophages (TAMs) toward a tumor-promoting M2 phenotype.”

    From Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer (2026) · cites this paper as [7]

    The Results section, “CD8+ T Cell-Dependent Long-Term Survival Benefit in Human Cancers” (page unavailable), describes a tumor microenvironment infiltrated by M2-type macrophages as immunosuppressive. But our copy does not say that efferocytosis clears apoptotic tumor cells or causes macrophages to polarize toward M2; searches for efferocytosis, apoptotic-cell clearance, and M2 polarization did not establish that mechanism. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The M2-like TAM phenotype supports tumor growth, angiogenesis, and immune evasion.

    “This phenotype supports tumor growth, angiogenesis, and immune evasion, creating a formidable barrier to effective antitumor immunity.”

    From Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer (2026) · cites this paper as [7]

    The Results section, “CD8+ T Cell-Dependent Long-Term Survival Benefit in Human Cancers” (page unavailable), describes a microenvironment infiltrated by M2-type macrophages as immune suppressive and predictive of poor survival. This supports the immune-evasion aspect, but the paper does not specifically say that M2-like macrophages support tumor growth or angiogenesis. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Manoharan, M., Mandloi, N., Priyadarshini, S., Patil, A., Gupta, R., Iyer, L., Gupta, R., & Chaudhuri, A.
Corresponding author
  • Gupta, Ravi
  • Chaudhuri, Amitabha
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-12-21
Volume
9
Pages
3017-3017
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.03017
PMC
PMC6308325
OpenAlex
W2906554396
Cited by
10
References
3
Citations by year
2025: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1
FWCI
0.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
tumor immune microenvironment, CD8+ T cells, PD-1, T cell exhaustion, CTLA-4, TIM-3, LAG-3, PI3K signaling, T cell receptor signaling, gene expression signatures, cancer prognosis, long-term survival, immune checkpoint inhibitors, tumor-infiltrating immune cells
MeSH terms
Hepatitis A Virus Cellular Receptor 2, Antineoplastic Agents, Immunological, Progression-Free Survival, Lymphocyte Activation Gene 3 Protein, Humans, Neoplasms, Prognosis, Signal Transduction, Antigens, CD, Gene Expression Regulation, Neoplastic, Lymphocytes, Tumor-Infiltrating, CD8-Positive T-Lymphocytes, Patient Selection, Computational Biology, Phosphatidylinositol 3-Kinases, Gene Expression Profiling, Kaplan-Meier Estimate, Tumor Microenvironment, CTLA-4 Antigen, Programmed Cell Death 1 Receptor, Datasets as Topic

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