TY - JOUR
T1 - Identification and characterisation of a group of cervical carcinoma patients with profound downregulation of intratumoral Type 1 (IFNγ) and Type 2 (IL-4) cytokine mRNA expression
AU - Gey, A.
AU - Kumari, P.
AU - Sambandam, A.
AU - Lecuru, F.
AU - Cassard, L.
AU - Badoual, C.
AU - Fridman, C.
AU - Nagarajan, B.
AU - Fridman, W. H.
AU - Tartour, E.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Type 1 cytokines, such as interferon gamma (IFNγ) 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 IFNγ 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 IFNγ, 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 IFNγ gene expression did not appear to be less infiltrated by T cells than control biopsies with measurable IFNγ 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.
AB - Type 1 cytokines, such as interferon gamma (IFNγ) 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 IFNγ 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 IFNγ, 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 IFNγ gene expression did not appear to be less infiltrated by T cells than control biopsies with measurable IFNγ 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.
UR - http://www.scopus.com/inward/record.url?scp=0037334155&partnerID=8YFLogxK
U2 - 10.1016/S0959-8049(02)00839-0
DO - 10.1016/S0959-8049(02)00839-0
M3 - Article
C2 - 12628838
AN - SCOPUS:0037334155
SN - 0959-8049
VL - 39
SP - 595
EP - 603
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 5
ER -