Interaction between the immune system and tongue squamous cell carcinoma induced by 4-nitroquinoline N-oxide in mice

Gallya Gannot*, Amos Buchner, Yona Keisari

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Squamous cell carcinoma of the oral cavity (SCC) accounts for 3% of cancers in the western world and 40% of cancers in India. The overall 5-year survival rate is only 50%. Most of the lesions appear intra-orally on the tongue. Results from a previous study demonstrated a significant increase in T and B-lymphocytes under the transformed epithelium when examining human lesions of hyperkeratosis, dysplasia and carcinoma of the tongue. In order to investigate the interaction between the host immunity and SCC, carcinogen induced SCC of the tongue was studied in mice. The water-soluble carcinogen, 4 nitroquinoline N-oxide (4NQO), was applied to BALB/c mice tongues and produced tongue SCC after a long incubation period of several months. Immunologic properties were examined systemically in the spleens and locally, at the tumor site. Examination of spleen lymphocytes from 4NQO induced mice revealed enlargement of the spleens and a significant decrease in the CD3, CD4, CD8 and CD19 cells. In the tongues, expression of TGF-β, TNF-α, GM-CSF, and IL-1β mRNA were detected. TNF-α protein was detected in the affected tongues using immunoassays. mRNA expression of TNF-α was detected in the cancerous epithelium when extracted from the connective tissue. CD11b and CD3 cells were detected in the connective tissue under the developing carcinoma. CD11b positive cells were more prominent. The infiltrate was very scattered and not prominent as the infiltrate in the human tongue tissues. These results indicate that the growing tumor affected the immune response around the tumor and systemically. Most of the cytokines, which appeared in the affected tongues, originated from the tumor surroundings, but TNF-α was found also in the tumor. The interaction between the tumor and immune response components is important for diagnosis and treatment purposes.

Original languageEnglish
Pages (from-to)287-297
Number of pages11
JournalOral Oncology
Issue number3
StatePublished - Mar 2004


  • 4NQO
  • Carcinoma
  • Cytokines
  • Immune infiltrate
  • Mice


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