Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 66, Issue 2, Pages 259-271Publisher
SPRINGER
DOI: 10.1007/s00262-016-1947-x
Keywords
MHC class I; Tumor-infiltrating lymphocytes; Immune escape; Tumor rejection; Tumor tissue architecture; PIVAC 15
Categories
Funding
- Instituto de Salud Carlos III - FEDER funds (European Union) [PI 11/1022, PI 11/1386, PI14/1978, PI16/00752, RETIC RD 06/020, RD09/0076/00165, PT13/0010/0039]
- Junta de Andalucia in Spain [CTS-143, PI09/0382]
Ask authors/readers for more resources
Most tumor cells derive from MHC-I-positive normal counterparts and remain positive at early stages of tumor development. T lymphocytes can infiltrate tumor tissue, recognize and destroy MHC class I (MHC-I)-positive cancer cells (permissive phase I). Later, MHC-I-negative tumor cell variants resistant to T-cell killing emerge. During this process, tumors first acquire a heterogeneous MHC-I expression pattern and finally become uniformly MHC-I-negative. This stage (phase II) represents a non-permissive encapsulated structure with tumor nodes surrounded by fibrous tissue containing different elements including leukocytes, macrophages, fibroblasts, etc. Molecular mechanisms responsible for total or partial MHC-I downregulation play a crucial role in determining and predicting the antigen-presenting capacity of cancer cells. MHC-I downregulation caused by reversible (soft) lesions can be upregulated by TH1-type cytokines released into the tumor microenvironment in response to different types of immunotherapy. In contrast, when the molecular mechanism of the tumor MHC-I loss is irreversible (hard) due to a genetic defect in the gene/s coding for MHC-I heavy chains (chromosome 6) or beta-2-microglobulin (B2M) (chromosome 15), malignant cells are unable to upregulate MHC-I, remain undetectable by cytotoxic T-cells, and continue to grow and metastasize. Based on the tumor MHC-I molecular analysis, it might be possible to define MHC-I phenotypes present in cancer patients in order to distinguish between non-responders, partial/short-term responders, and likely durable responders. This highlights the need for designing strategies to enhance tumor MHC-I expression that would allow CTL-mediated tumor rejection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available