Related Experiment Video

Updated: Oct 15, 2026

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
07:18

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts

Published on: June 13, 2019

Functional deficiencies of components of the MHC class I antigen pathway in human tumors of epithelial origin

K Delp1, F Momburg, C Hilmes

  • 1The Johannes Gutenberg-University, IIIrd Department of Internal Medicine, Mainz, Germany.

Bone Marrow Transplantation
|August 10, 2000
PubMed

Insights

Human tumor cells show deficiencies in the MHC class I antigen processing machinery (APM), leading to reduced immune recognition. Interferon-gamma treatment restored APM function and MHC class I expression, suggesting immune evasion strategies in cancer.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Oncogenic transformation in mice is linked to reduced MHC class I antigen processing machinery (APM) components.
  • Investigating this association in human cancers is crucial for understanding immune evasion.

Purpose of the Study:

  • To determine if human tumor cell lines with altered ras protein exhibit similar APM component repression as observed in murine models.
  • To analyze the expression of various APM components in human tumor cell lines of distinct histology.

Main Methods:

  • Utilized Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot analyses.
  • Analyzed expression of MHC class I antigens, TAP, proteasome subunits, PA28, calnexin, calreticulin, and tapasin.
  • Assessed the impact of Interferon-gamma (IFN-γ) treatment on APM components and MHC class I expression.

Main Results:

  • Eleven of twelve human tumor cell lines displayed deficiencies in TAP, LMP2, LMP10, and/or tapasin.
  • Expression of calnexin, calreticulin, beta2-microglobulin, LMP7, and PA28alpha remained largely unaltered.
  • Impaired APM components led to reduced MHC class I surface expression, particularly HLA-A and HLA-B haplotypes.
  • IFN-γ treatment corrected deficiencies and increased MHC class I antigen levels.

Conclusions:

  • Dysregulation of APM components, rather than structural alterations, is a potential mechanism for immune evasion in colon, small cell lung, and pancreatic carcinoma cell lines.
  • Targeting APM dysregulation could offer therapeutic strategies for enhancing anti-tumor immunity.

More Related Videos

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors15:24

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

Published on: December 16, 2022

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development11:02

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Published on: October 30, 2013

Related Concept Videos

Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...