Type 1 cytokines, such as interferon gamma (IFNgamma) and interleukin-2 (IL-2), increase
T cell-mediated immune responses and are considered to be beneficial for antitumour
immunity. Type 2 cytokines, such as IL-4, IL-5, and IL-10, inhibit Type 1 responses
and promote humoral responses. We have previously reported an association between
low intratumoral IFNgamma mRNA levels and poor clinical outcome in patients with invasive
cervical carcinoma. In this study, by using quantitative polymerase chain reaction
(PCR), we identified a group of cervical carcinoma patients with undetectable intratumoral
T cell-derived cytokine mRNAs, as IFNgamma, IL-4 and IL-17 expression could not be
detected in 5, 25 and 8 of the 52 biopsies analysed, respectively. Global downregulation
of Type 1 and Type 2 cytokines was observed in a subgroup of patients who more frequently
presented advanced stage tumours. Biopsies of patients with no IFNgamma gene expression
did not appear to be less infiltrated by T cells than control biopsies with measurable
IFNgamma gene expression. These results clearly demonstrate that, in some clinical
situations, the decrease in intratumoral Type 1 cytokines is not associated with a
Type 2 polarisation, but rather reflects global deactivation of T cells at the tumour
site. These data provide support for immunotherapy protocols designed to reverse the
anergic state of T cells in cancer.