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Cited by 48Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

The role of immune checkpoints in antitumor response: a potential antitumor immunotherapy

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Mejía-Guarnizo, Lidy Vannessa, Monroy-Camacho, Paula Stefany, Turizo-Smith, Andrés David, Rodríguez-García, Josefa Antonia·2023·Frontiers in Immunology
DOI 10.3389/fimmu.2023.1298571PMC PMC10757365
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Abstract

Immunotherapy aims to stimulate the immune system to inhibit tumor growth or prevent metastases. Tumor cells primarily employ altered expression of human leukocyte antigen (HLA) as a mechanism to avoid immune recognition and antitumor immune response. The antitumor immune response is primarily mediated by CD8+ cytotoxic T cells (CTLs) and natural killer (NK) cells, which plays a key role in the overall anti-tumor immune response. It is crucial to comprehend the molecular events occurring during the activation and subsequent regulation of these cell populations. The interaction between antigenic peptides presented on HLA-I molecules and the T-cell receptor (TCR) constitutes the initial signal required for T cell activation. Once activated, in physiologic circumstances, immune checkpoint expression by T cells suppress T cell effector functions when the antigen is removed, to ensures the maintenance of self-tolerance, immune homeostasis, and prevention of autoimmunity. However, in cancer, the overexpression of these molecules represents a common method through which tumor cells evade immune surveillance. Numerous therapeutic antibodies have been developed to inhibit immune checkpoints, demonstrating antitumor activity with fewer side effects compared to traditional chemotherapy. Nevertheless, it's worth noting that many immune checkpoint expressions occur after T cell activation and consequently, altered HLA expression on tumor cells could diminish the clinical efficacy of these antibodies. This review provides an in-depth exploration of immune checkpoint molecules, their corresponding blocking antibodies, and their clinical applications.

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  • HLA variation and expression levels are important determinants of ICI response.

    “Multiple reviews and original research studies have indicated that HLA variation and expression levels are important determinants of ICI response.”

    From PathTIGR: A pathway topology-informed graph representation learning framework for immunotherapy response prediction (2026) · cites this paper as [52]

    The Histocompatibility leukocyte antigen-G section (page not available) says heterogeneous HLA-G expression in tumors is probably an obstacle to clinical response to immune checkpoint inhibitors. It also notes HLA-G polymorphism as a possible reason expression varies, but does not establish that HLA variation broadly determines ICI response. The claim is broader and more definite than the review's account. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • HLA has been identified as a biomarker for predicting ICI response, with higher expression observed in responders.

    “HLA has been identified as a biomarker for predicting ICI response, with higher expression observed in responders (51–53).”

    From PathTIGR: A pathway topology-informed graph representation learning framework for immunotherapy response prediction (2026) · cites this paper as [52]

    The Histocompatibility leukocyte antigen-G section links heterogeneous HLA-G expression to clinical response to immune checkpoint inhibitors. It does not identify HLA expression as a validated predictive biomarker or report higher expression in responders; it also discusses HLA-G specifically, rather than HLA generally. No page number is available in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Mejía-Guarnizo, L. V., Monroy-Camacho, P. S., Turizo-Smith, A. D., & Rodríguez-García, J. A.
Affiliations
  • Universidad Nacional de Colombia (CO)
  • Instituto Nacional de Cancerología (CO)
Corresponding author
Rodríguez-García, Josefa Antonia
ORCID
Mejía-Guarnizo, Lidy Vannessa
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2023-12-15
Volume
14
Pages
1298571-1298571
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2023.1298571
PMC
PMC10757365
OpenAlex
W4389793945
Cited by
48
References
8
Citations by year
2026: 22 · 2025: 20 · 2024: 6
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (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 › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
immune checkpoint, antitumor immunity, cancer immunotherapy, immune checkpoint inhibitors, HLA downregulation, tumor immune evasion, CD8+ cytotoxic T lymphocytes, natural killer cells, T cell receptor signaling, T cell activation, blocking antibodies, immune tolerance
MeSH terms
Antibodies, HLA Antigens, Humans, Immunotherapy, Killer Cells, Natural, Neoplasms, T-Lymphocytes, Cytotoxic, Histocompatibility Antigens Class I

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