Immune Escape Associated with Functional Defects in Antigen-Processing Machinery in Head and Neck Cancer

Abstract

Recent revival of interest in the role of immune surveillance in the pathogenesis and control of malignant diseases has focused attention on escape mechanisms used by tumor cells to evade immune recognition. Defects in the host's tumor antigen^specific immune responses and abnormalities in tumor cell expression of HLA class I molecules and tumor antigen are known to contribute to tumor progression. However, the mechanism(s) responsible for the lack of tumor cell recognition by functional HLA class I antigen^restricted, tumor antigen^specific CTLs despite expression of the restricting HLA class I allele and targeted tumor antigen by tumor cells remain(s) unexplained. In squamous cell carcinomas of the head and neck (SCCHN), this type of tumor escape is a rule rather than the exception. Here, we discuss evidence pointing to functional defects in the antigen-processing machinery as one mechanism underlying resistance of SCCHN cells to recognition and lysis by HLA class I antigen^restricted, tumor antigen^specific CTL. In addition, based on the restoration by IFN-g of SCCHN cell sensitivity to recognition by these CTL, we suggest strategies that may improve the clinical course of the disease by enhancing susceptibility of malignant cells to immune recognition.

Active Antiviral T-Lymphocyte Response Can Be Redirected against Tumor Cells by Antitumor Antibody × MHC/Viral Peptide Conjugates

“…In contrast, peptides derived from autologous tumor or differentiation antigens are often not sufficiently expressed on tumor cells because they have to compete against numerous normal cellular peptides for transport to the endoplasmic reticulum and presentation through binding to MHC molecules, and functional defects in the antigen processing delivery of some tumors have been recently reported (7).…”

“…It is hard to understand the reasons for the relatively poor antitumor activity of the induced specific T lymphocytes, given that such effector cells are known to be so efficient in the elimination of virus-infected cells and in allograft rejection. Three major explanations have been given for the inefficiency of the T-cell antitumor response: the poor antigenicity of autologous tumor antigens, the low expression or absence of MHC molecules on the tumor cell surface, or some functional defects in their antigen-processing machinery (6,7).…”

How tumours escape mass destruction

“…A frequent abnormality observed in many tumour cells involves alterations in the expression of MHC molecules or in the components of the Ag-processing pathways (Ferris et al, 2006;Lopez-Albaitero et al, 2006;Chang and Ferrone, 2007). Tumour cells can develop mutations that result in the misprocessing or mispresenting of TAA so that an appropriate Ag-presenting complex (MHC-b 2 microglobulin/peptide) does not form, or cannot be recognized, on the tumour cell surface.…”

Secretion of inflammatory and regulatory cytokines and the association with depth and type of tumour invasion in patients with cancer of the larynx

“…14; 6 (355-362) tworowym różnego pochodzenia. Badania nad tymi zagadnieniami stają się obecnie wiodące w immunopatologii klinicznej i wyznaczają kierunek poszukiwań dla wskazania immunologicznych markerów agresywności nowotworu [15,18,19,[23][24][25][26][27][28][29][30][31][32].…”