ArticleOncotarget2016
Squamous cell carcinomas escape immune surveillance via inducing chronic activation and exhaustion of CD8+ T Cells co-expressing PD-1 and LAG-3 inhibitory receptors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04150900 (1922GCCC), which is not on this map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
1922gccc: phase 2 study of pembrolizumab and bavituximab for progressive recurrent/metastatic squamous cell carcinoma of the head and neck
Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
- Multifactorial effects of LGALS1 blockade sensitize tumors to immune checkpoint inhibitor.Experimental hematology & oncology · 2026Article
- Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Advanced Cutaneous Squamous Cell Carcinoma: Biology, Immunotherapy, and Evolving Prognostic Factors.Biomedicines · 2025Review
- The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas.Signal transduction and targeted therapy · 2024Article
- Oral Pre-malignancy: An Update on Novel Therapeutic Approaches.Current oncology reports · 2024Review
- The Aryl Hydrocarbon Receptor Controls IFNγ-Induced Immune Checkpoints PD-L1 and IDO via the JAK/STAT Pathway in Lung Adenocarcinoma.bioRxiv : the preprint server for biology · 2024Article
- Review
- Granzyme F: Exhaustion Marker and Modulator of Chimeric Antigen Receptor T Cell-Mediated Cytotoxicity.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Review
- Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview.Medical oncology (Northwood, London, England) · 2023Review
- Exploring animal models in oral cancer research and clinical intervention: A critical review.Veterinary medicine and science · 2023Review
- Monoclonal antibodies for the treatment of squamous cell carcinoma: A literature review.Cancer reports (Hoboken, N.J.) · 2023Review
- Global research trends in immunotherapy for head and neck neoplasms: A scientometric study.Heliyon · 2023Article
- Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders.Frontiers in immunology · 2023Article
- Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways.Molecules (Basel, Switzerland) · 2022Review
- Divergent outcomes of anti-PD-L1 treatment coupled with host-intrinsic differences in TCR repertoire and distinct T cell activation states in responding versus non-responding tumors.Frontiers in immunology · 2022Article
- Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors.Frontiers in oncology · 2022Review
- Current status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2022Review
- Overcoming Resistance to Checkpoint Inhibitors: Natural Killer Cells in Non-Small Cell Lung Cancer.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Squamous cell carcinoma (SCC) is the second commonest type of skin cancer. Moreover, about 90% of head and neck cancers are SCCs. SCCs develop at a significantly higher rate under chronic immunosuppressive conditions, implicating a role of immune surveillance in controlling SCCs. It remains largely unknown how SCCs evade immune recognition. Here, we established a mouse model by injecting tumor cells derived from primary SCCs harboring KrasG12D mutation and Smad4 deletion into wild-type (wt) or CD8-/- recipients. We found comparable tumor growth between wt and CD8-/- recipients, indicating a complete escape of CD8+ T cell-mediated anti-tumor responses by these SCCs. Mechanistically, CD8+ T cells apparently were not defective in infiltrating tumors given their relatively increased percentage among tumor infiltrating lymphocytes (TILs). CD8+ TILs exhibited phenotypes of chronic activation and exhaustion, including overexpression of activation markers, co-expression of programmed cell death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), as well as TCRβ downregulation. Among CD4+ TILs, T regulatory cells (Tregs) were preferentially expanded. Contradictory to prior findings in melanoma, Treg expansion was independent of CD8+ T cells in our SCC model. Unexpectedly, CD8+ T cells were required for promoting NK cell infiltration within SCCs. Furthermore, we uncovered AKT-dependent lymphocyte-induced PD-L1 upregulation on SCCs, which was contributed greatly by combinatorial effects of CD8+ T and NK cells. Lastly, dual blockade of PD-1 and LAG-3 inhibited the tumor growth of SCCs. Thus, our findings identify novel immune evasion mechanisms of SCCs and suggest that immunosuppressive mechanisms operate in a cancer-type specific and context-dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.