High Number of Intraepithelial CD8 super(+) Tumor-Infiltrating Lymphocytes Is Associated with the Absence of Lymph Node Metastases in Patients with Large Early-Stage Cervical Cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2007-01, Vol.67 (1), p.354-361
• Main Authors: Piersma, Sytse J, Jordanova, Ekaterina S, van Poelgeest, Marieette IE, Kwappenberg, Kitty MC, van der Hulst, Jeanette M, Drijfhout, Jan W, Melief, Cornelis JM, Kenter, Gemma G, Fleuren, Gert Jan, Offringa, Rienk, van der Burg, Sjoerd H
• Format: Article
• Language: English
• Subjects: Human papillomavirus
• ISSN: 0008-5472

In a prospective study, we have examined the tumor-specific immune response in a group of 59 patients with human papillomavirus (HPV) 16-positive (HPV16 super(+))-induced or HPV18 super(+)-induced cervical cancer. Local antitumor immunity was analyzed by the enumeration of tumor-infiltrating dendritic cells and CD4 super(+), CD8 super(+), and regulatory T cells as well as by calculation of the ratio of CD8 super(+)/CD4 super(+) T cells and CD8 super(+)/regulatory T cells. Systemic tumor-specific immunity was assessed by determination of the HPV E6- and/or E7-specific T-cell response in the blood of these patients. Finally, these variables were evaluated with respect to known histopathologic prognostic variables, including the absence (LN super(-)) or presence (LN super(+)) of lymph node metastases. Stratification according to the lymph node status of patients revealed a significantly stronger CD8 super(+) T-cell tumor infiltration, a higher CD8 super(+)/CD4 super(+) T-cell ratio, and higher CD8 super(+)/regulatory T-cell ratio in the group of patients in which the tumor failed to metastasize to the tumor-draining lymph node. Subdivision according to the presence (IR super(+)) or absence (IR super(-)) of circulating HPV-specific T cells disclosed that the highest number of tumor-infiltrating CD8 super(+) T cells was found in the group of LN super(-) patients displaying a concomitant systemic tumor-specific immune response (LN super(-)IR super(+)). CD8 super(+) T-cell infiltration in LN super(-)IR super(-) patients was comparable with that of LN super(+) patients. In cervical cancer, the absence of lymph node metastases is strongly associated with a better prognosis. Our data indicate that, especially in a subgroup of LN super(-) patients, a strong and effective interaction between immune system and tumor exists. This subgroup of cervical cancer patients may have the best prognosis. [Cancer Res 2007; 67(1):354-61]