Disregulation in TH1 and TH2 subsets of CD4 + T cells in peripheral blood of colorectal cancer patients and involvement in cancer establishment and progression

Abstract

Recent theories have established that, during an ongoing immune response, the lymphokines produced by TH1 and TH2 subsets of CD4+ T cells are critical to the effectiveness of that response. In vivo and in vitro studies have demonstrated that the type of environmental cytokines plays a determinant role in directing the development of naive T cells into TH1 or TH2 effector cells. Disregulated expansion of one or other subset may contribute to the development of certain diseases. To establish whether a similar situation might exist in the cells of the peripheral blood (PBMC) of colorectal cancer patients, we have performed immunological studies on a group of patients and a group of healthy subjects. We examined the interleukin-2 (IL-2), interferon gamma (IFNgamma), IL-4, IL-6 and tumour necrosis factor alpha levels in serum; the production of IL-4 and IL-2, with and without activating agents, by PBMC, tumour-draining lymph node lymphocytes and tumour cells; and the proliferative response of PBMC to IL-2, IL-4 and anti-CD3 monoclonal antibody (anti-CD3), which were variously combined. The data of the present study lead us to hypothesize that, because of suppressive effects probably due to environmental IL-4, in the peripheral blood of patients there seems to be a disregulation in the functionality of TH1 and TH2 subsets of CD4+ T cells, with an expansion in TH2 and a malfunction in TH1 cells. Moreover it seems that this disregulation increases with as the disease progresses through the stages, suggesting that it can be directly implicated in the mechanisms that allow the tumour to locate and progress in the host.

Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette–Guérin (BCG) in patients with superficial bladder cancer

“…The type of immune response might be influenced by the neoplasia as well. Indeed, Pellegrini et al showed that in peripheral blood cells of patients with colorectal cancer, there was a dysregulation in the functionality of Th1 and Th2 cells, with an expansion in Th2 and a malfunction in Th1 cells [29]. It is of note that we observed no correlation between the evolution in cellular immune response directed against tuberculin and the clinical outcome of patients treated with BCG instillations [8].…”

Vector-Encoded Helicobacter pylori Neutrophil-Activating Protein Promotes Maturation of Dendritic Cells with Th1 Polarization and Improved Migration

“…Usually, the tumor microenvironment is immunosuppressive, with presence of IL-10 and TGF-b, which induces regulatory T cell responses and reduces the prevalence of Th1 CD4 + T cells. This shifts the Th1/Th2 immune balance, and the immunosuppressive nature of these cells can lead to tolerance against tumor Ags or pathogens (43,44). IL-10 2/2 mice, compared with wild-type mice, develop severe gastritis when infected with H. pylori bacteria; therefore, IL-10 may have a potential role in downregulating H. pylori-induced inflammation at the site of infection (45).…”

Significance and Outlook of Preoperative Serum Interleukin-1β and Interleukin-6 as Prognostic Factors in Esophageal Cancer

“…It has also been reported that there is decreased IL-2 production and elevated IL-4, IL-6, and IL-10 production in colorectal cancer, decreased IL-2 and IFN-γ production in bladder cancer, prostate cancer, and renal cancer and increased IL-10 mRNA expression in lung cancer [8,[14][15][16][17]. Expression of the Th2 type cytokine IL-6 within esophageal cancer tissue is known to be profoundly associated with the progression of esophageal cancer and poor prognosis [18,19].…”