Prognostic significance of cytokine modulation in non‐small cell lung cancer

Abstract

Increased production of immunosuppressive interleukin-10 (IL-10) by non-small cell lung cancer (NSCLC) and increased serum IL-10 concentrations in NSCLC-patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL-2 secretion in whole blood cell cultures of NSCLC-patients. We now analyzed the influence of IL-2 secretion on survival in NSCLC-patients and the influence of IL-10 on IL-2 secretion. The correlation of the IL-2 producing ability of whole blood cells in response to PHA in 90 NSCLC-patients at the time of diagnosis to survival was calculated by Crit-level, the Kaplan-Meier method and the log-rank test. With a cut-off value of IL-2 production of 1,100 pg/ml by whole blood cells the difference in survival was significant with a p-value of 0.014. In the group with high and low IL-2, median survival was 14.1 and 9.7 months, respectively. In the subgroup of 33 surgically-treated patients the difference in survival was significant with a p-value of 0.011. In 14 patients with surgical resection of the tumor and high IL-2 at diagnosis and 19 patients with surgical resection, but low IL-2 at diagnosis, median survival was 86.2 and 11.3 months, respectively. Secretion of IL-2 in whole blood cell cultures from healthy individuals was inhibited in a dosedependent manner upon addition of IL-10. Taken together, suppression of IL-2 secretion has prognostic significance for survival of NSCLC-patients and may be mediated by tumorderived IL-10.

Tumour-associated macrophages in nonsmall cell lung cancer: the role of interleukin-10

“…In fact, although it is commonly regarded as an antiinflammatory, immunosuppressive cytokine, IL-10 also possesses immunostimulating properties [23]. These conflicting biological data may explain the contradictory results found on the prognostic relevance of IL-10 expressed by lung cancer cells [8,12,13,31].…”

A pooled analysis of the IL-10-1082 A/G polymorphism and the nasopharyngeal carcinoma susceptibility

“…It is generally involved in antigen presentation, macrophage activation, B cell proliferation, antigen-specific T-cell proliferation, and cytokine production. In addition to the critical role of IL10 in immune response, there is evidence that IL10 may be associated with tumor development and metastasis [12,13]. Increased serum levels of IL-10 have been reported in patients with head and neck carcinomas, including NPC [14][15][16].…”

Phase I Trial of TGF-β2 Antisense GM-CSF Gene-Modified Autologous Tumor Cell (TAG) Vaccine

“…Tumor-infiltrating lymphocytes (TIL) include immunosuppressive regulatory T cells (Treg; CD4 þ CD25 þ Fox3p þ ; ref. 9) which, rather than cross-priming CD8 þ cytotoxic T cells, inhibit T-effector antitumor activities (9)(10)(11) in part through TGFb-dependent suppression of antigen-presenting dendritic cell (DC) processes (12). Further, both tumor-infiltrating, tolerogenic DCs and suppressor T lymphocytes express the TGF-b receptor 1 (TGF-bR1) and are therefore susceptible to immunosuppressive modulations by TGF-b1 and TGFb2 produced by tumor cells (13)(14)(15)(16)(17)(18).…”