Cancer-induced defective cytotoxic T lymphocyte effector function: another mechanism how antigenic tumors escape
1Department of Cell Biology and Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA.
Background:
The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Decreased levels of enzymes involved with T-cell signal transduction have been reported by several laboratories, suggesting that tumors or host cells recruited to the tumor site actively down-regulate antitumor T-cell immune response. This permits tumor escape from immune-mediated killing. The possibility that defects in T-cell signal transduction can be reversed, which would potentially permit successful vaccination or adoptive immunotherapy, motivates renewed interest in the field. Summarizing the literature concerning tumor-induced T-cell dysfunction, we focus on the end stage of immune response to human cancer, that of defective cytotoxic T lymphocyte killing function. Based on the data from several laboratories, we hypothesize a biochemical mechanism that accounts for the unusual phenotype of antitumor T-cell accumulation in tumors, but with defective killing function.
Insights
Tumors can impair T-cell immune responses by causing biochemical defects in these cells. Understanding these defects in cytotoxic T lymphocytes could lead to new cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Tumor growth is linked to impaired immune cell function, particularly T lymphocytes infiltrating cancers.
- Biochemical defects in T-cell signal transduction are observed, suggesting tumors actively suppress anti-tumor responses.
- Reversing these T-cell defects may enable effective cancer vaccination and immunotherapy.
Purpose of the Study:
- To review and synthesize existing literature on tumor-induced T-cell dysfunction.
- To focus on the impaired cytotoxic T lymphocyte killing function in human cancers.
- To propose a biochemical mechanism for T-cell dysfunction in the tumor microenvironment.
Main Methods:
- Literature review and synthesis of experimental data from multiple laboratories.
- Analysis of biochemical defects in T lymphocytes within tumor tissues.
- Hypothesizing a biochemical mechanism for observed T-cell phenotypes.
Main Results:
- Accumulation of T lymphocytes within tumors is often accompanied by defective killing function.
- Evidence suggests tumor cells or associated host cells actively down-regulate T-cell responses.
- Specific enzyme deficits in T-cell signaling pathways are implicated in immune suppression.
Conclusions:
- Tumor-induced T-cell dysfunction, specifically impaired cytotoxic activity, is a critical factor in tumor immune evasion.
- A proposed biochemical mechanism explains the paradoxical presence of non-functional T cells in tumors.
- Further research into reversing these defects holds promise for enhancing cancer immunotherapy.
More Related Videos
Related Concept Videos
01:40Cell-mediated Immune Responses
02:17The Tumor Microenvironment
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:27Tumor Immunotherapy