High Frequency of Cancer Patients with Abnormal Assembly of the T Cell Receptor‐CD3 Complex in Peripheral Blood T Lymphocytes

Abstract

Structural abnormality of T cell receptor (TCR)‐CD3 complex on the cell surface was investigated in peripheral blood lymphocytes (PBL) from 55 cancer patients. In 24 of the 68 tests done on these patients, the CD3C chain was not detected by immunoprecipitation with anti‐CD3ζ monoclonal antibody (mAb), but was observed with anti‐CD3ζ mAb, suggesting that a high frequency of cancer patients possesses abnormal T cell receptor (TCR) complex in PBL. On the other hand, the total ζ chain was missing in several advanced cases. During follow‐up of several patients, the ζ chain became undetectable after two or three months of cancer progression. It appears that immunosuppressive status can be monitored by analyzing the TCR‐CD3 complex on the cell surface of PBL.

Expression and Signal Transduction of T‐Cell Antigen Receptor (TCR)/CD3 Complexes on Fresh or In Vitro Expanded T Lymphocytes from Patients with Hodgkin's and Non‐Hodgkin's Lymphomas

“…In conclusion, the defective T-cell responses in the lymphoma patients were caused by two dysfunctions: (1) a decreased number of TCR/CD3 þ T-cells and (2) a diminished signal transmission in the residual TCR/CD3 þ T-cells. It should be noted that we obtained the same results with T-cells from seven HD lymph nodes, indicating that our results with peripheral T-cells reflect the situation in or around the tumour site [15].…”

“…The number of membrane TCR/CD3 complexes appears directly proportional to the degree of T-cell activation [11] even though few TCR/CD3 complexes seem involved in the actual triggering event(s) [50]. Dysfunction of T-cell activation has been observed in acquired or inhereted immunodeficiencies [51,52,53], in autoimmune diseases [54,55], or in certain types of cancer [12][13][14][15][16].…”

“…Saito and co-workers [15,39] have shown that T-cells from tumour-bearing patients could express membrane TCR/CD3 complexes, which lacked z 2 homodimers or where z 2 homodimers were replaced with FCRg chains. T-cells with FCR replacing z 2 homodimers seem to be less easily activated compared to normal T-cells [40].…”

“…Several possible mechanisms can explain the failure to control tumour cell growth: (1) lack of recognition of tumour cell antigens; (2) induction of T-cell anergy; (3) absence of secondary stimuli necessary for T-cell activation (CD28, etc. ); (4) expression of lower numbers of TCR/CD3 complexes on the T-cell surface membrane; (5) expression of nonfunctional TCR complexes at the membrane; (6) TCR complexes are not or insufficiently connected with the intracellular protein-kinases [6][7][8][9][10][11][12][13][14][15][16]; (7) decrease or lack of expression of major histocompatibility complex (MHC) class I molecules [17].…”

Mice Bearing Late-Stage Tumors Have Normal Functional Systemic T Cell Responses In Vitro and In Vivo

“…TCR has been recently shown to be a substrate for cleavage by caspase 3 resultant from activation of Fas, implying a mechanism by which TIL could be rendered dysfunctional by cell-to-cell contact in the tumor microenvironment (32). In this regard, there have been several reports that PBL T cells of patients with certain cancers also have decreased TCR levels, implying that systemic T cells are dysfunctional in cancer patients (33)(34)(35). If TCR is degraded in TIL by a Fas-dependent mechanism requiring contact with tumor, as suggested by the data presented by Rabinowich et al (31), how TCR in PBL T cells could be degraded is hard to envisage, because this would mean that the whole body complement of T cells would have to have ϩ and CD8 ϩ T cells were isolated by magnetic immunobeading from splenocyte preparations of individual tumor-bearing or control mice, and aliquots were plated in the presence of plate-bound anti-TCR (MCA-38) or anti-TCR plus anti-CD28 Abs for 48 h (2 ϫ 10 6 cells/ml) as described in Materials and Methods.…”