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Prognostic Value of Tumor-Infiltrating CD4⁺ T-Cell Subpopulations in Head and Neck Cancers

Authors' Affiliations: ¹ Institut National de la Sante et de la Recherche Medicale U255 and ² Plateau technique d'imagerie cellulaire, IFR58, Institut Biomedical des Cordeliers, Université Paris 5; ³ Unité d'Anatomie Pathologique, ⁴ Department of Otorhinolaryngology-Head and Neck Surgery, and ⁵ Unité d'Immunologie Biologique, Hopital Européen Georges Pompidou; ⁶ Departments of Otorhinolaryngology-Head and Neck Surgery and ⁷ Biostatistics, Institut Curie; and ⁸ Centre d'Investigations Cliniques 9201, Assistance Publique des Hopitaux de Paris, Paris, France

Requests for reprints: Eric Tartour, Unité d'Immunologie Biologique, Hopital Européen Georges Pompidou, 20 Rue Leblanc, 75908 Paris Cedex 15, France. Phone: 33-1-56-09-39-42; Fax: 33-1-56-09-20-80; E-mail: eric.tartour{at}hop.egp.ap-hop-paris.fr.

Purpose: CD4⁺ T cells play a central role in initiating and maintaining anticancer immune responses. However, regulatory CD4⁺CD25⁺ T cells which express Foxp3 have also been shown to inhibit antitumor effector T cells. In view of these heterogeneous CD4⁺ T-cell populations, this study was designed to determine the prognostic value of various tumor-infiltrating CD4⁺ T-cell populations in head and neck squamous cell carcinoma.

Experimental Design: Eighty-four newly diagnosed untreated patients with histologically proven primary head and neck squamous cell carcinoma were included in this study. Double or triple immunofluorescence staining was done to assess and quantify the activated CD4⁺CD69⁺ T cells, regulatory CD4⁺Foxp3⁺ T cells, and mixed CD4⁺CD25⁺ T cells comprising both activated and regulatory T cells.

Results: On univariate analysis, high levels of tumor-infiltrating CD4⁺CD69⁺ T cells were correlated with both better locoregional control (P = 0.01) and longer survival (P = 0.01). Infiltration by regulatory Foxp3⁺CD4⁺ T cells was positively associated with a better locoregional control of the tumor. Multivariate analysis showed that the only significant prognostic factors related to locoregional control were T stage (P = 0.02) and CD4⁺Foxp3⁺ T-cell infiltration of the tumor (P = 0.02). In the Cox multivariate analysis, only two variables influenced overall survival probability: T stage (P = 0.036) and CD4⁺CD69⁺ T-cell infiltration (P = 0.017).

Conclusion: This study shows that tumor-infiltrating activated CD4⁺CD69⁺ T cells are associated with a good prognosis in head and neck squamous cell carcinoma. In addition, regulatory Foxp3⁺CD4⁺ T cells are positively correlated with locoregional control may be through down-regulation of harmful inflammatory reaction, which could favor tumor progression.

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