Immune Suppression and Colorectal Cancer

C. Evans; A. G. Dalgleish; D. Kumar

Disclosures

Aliment Pharmacol Ther. 2006;24(8):1163-1177. 

In This Article

Regulatory T Cells

Regulatory T (Treg) cells are functionally defined as T cells that inhibit immune responses by influencing the activity of another cell type. They are a small subset (10%) of thymus-derived CD4+ T cells that co-express the CD25 antigen (the IL-2R α-chain) and control immune responses to autoantigens.[197] They are essential for immune system homeostasis[198] and play a critical role in the prevention of organ-specific autoimmunity and allograft rejection.[199] Their suppression of autoreactive T cells helps prevent autoimmune disorders[200,201,202] but also dampens antitumour responses by suppressing TAA-specific immunity.[203]

Treg cells suppress immune responses through the action of immunosuppressive cytokines (e.g. IL-10 and TNF-β) and/or via a cell contact.[204] They inhibit the proliferation and cytokine production of antigen-specific CD4+ or CD8+ T cells,[205] inhibit NK cell-mediated cytotoxicity,[206] and inhibit both DC maturation and antigen presenting function.[207]

Wolf et al. demonstrated a significant increase (2.5-fold) in Treg cells in the peripheral blood of 42 patients with malignant tumours (nine of whom had colorectal cancer).[206] High levels of Treg cells have been identified in lung, ovarian, breast and pancreatic tumour specimens.[197] Treg cells contribute to the growth of human tumours in vivo having been specifically recruited by both tumour cells and microenvironmental macrophages.[203] Rat colon cancer tumour volume is correlates with an expansion of Treg cells[208] plus tumour-specific CD4+ T cells which emerge in the absence of Treg cells are able to reject CT26 colon cancer cells.[209]

Treg cell depletion allows the immune system to mount an efficient antitumoural immune response against poorly immunogenic tumours[209] plus therapies which manipulate their regulatory mechanisms may evoke effective tumour immunity in otherwise non-responsive animals.[210] It may be that suppression of Treg cells allows other therapies to be more potent in their action. For example, a translational phase II trial investigating the treatment of colorectal carcinoma patients using combined chemo-immunotherapy [gemcitabine + FOLFOX-4 (oxaliplatin, fluorouracil and folinic acid) polychemotherapy followed by the subcutaneous administration of granulocyte macrophage colony-stimulating factor and low-dose IL-2] found a high objective response (68.9%) and disease control rates (96.5%) with an enhanced proliferative response to colon carcinoma antigen and a significant reduction in Treg cells.[211]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....