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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Targeted Cancer Therapies02:57

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Related Experiment Video

Updated: Sep 13, 2025

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Resolution of Squamous-Cell Carcinoma by Restoring T-Cell Receptor Signaling.

Peiying Ye1, Jenna R E Bergerson2, Isaac Brownell3

  • 1Laboratory of Immunoregulation and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD.

The New England Journal of Medicine
|July 31, 2025
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Summary

This study reveals beta-human papillomavirus (β-HPV) directly causes skin cancer in individuals with T-cell receptor (TCR) signaling defects. Restoring TCR signaling resolved HPV-related diseases, highlighting β-HPV

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Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Cutaneous squamous-cell carcinoma (SCC) is linked to ultraviolet radiation, with beta-human papillomavirus (β-HPV) considered a minor contributor.
  • Defects in T-cell receptor (TCR) signaling impair adaptive immunity, potentially influencing HPV-related oncogenesis.

Purpose of the Study:

  • To investigate the role of β-HPV in skin carcinogenesis in a patient with a genetic T-cell signaling defect.
  • To determine if restoring T-cell function can resolve HPV-related diseases.

Main Methods:

  • Case study of a patient with invasive cutaneous SCC, β-HPV19 integration, and ZAP70 deficiency.
  • Analysis of TCR signal transduction pathways.
  • Treatment with allogeneic hematopoietic-cell transplantation.

Main Results:

  • The patient presented with recurrent, unresectable cutaneous SCC and other HPV-related conditions.
  • Genomic integration of β-HPV19 was detected in the SCC.
  • Successful allogeneic hematopoietic-cell transplantation restored TCR signaling and led to complete resolution of all HPV-related diseases.

Conclusions:

  • β-HPV plays a direct role in skin carcinogenesis in immunocompromised individuals with defective adaptive T-cell responses.
  • Restoration of T-cell receptor signaling is crucial for controlling β-HPV-driven diseases.
  • This case challenges the view of β-HPV as a dispensable cofactor in cutaneous SCC.