MHC Class-I Loss and Cancer Immune Escape

This book is about the escape strategies used by cancer cells to avoid the immune response of the host. The main characters of this story are the "Antigen Presenting Molecules" and the "T Lymphocytes". The former are known as the Major Histocompatibility Complex (MHC): the H-2 and the HLA molecules. The latter are a subgroup of white cells travelling all over our body which are capable to distinguish between "self and non self".

Readers will know from the inside about the history of the HLA genetic system and will discover how T lymphocytes recognize and destroy cancer cells. One of the key important questions is: Why tumors arise, develop and metastasize? This book tries to answer this question and will explain how cancer cells become invisible to killer T lymphocytes. The loss of the HLA molecules is a major player in this tumor escape mechanism.

Cancer immunotherapy is aimed at stimulating T lymphocytes to destroy tumor cells. However, the clinical response rate is not as high as expected. The molecular mechanisms responsible for MHC/HLA antigen loss play a crucial role in this resistance to immunotherapy. This immune escape mechanism will be discussed in different types of tumors: lung, prostate, bladder and breast...ect. as well as melanoma and lymphoma.

This book will be useful to Oncologists, Pathologists and Immunologist that will enter this fascinating area of research. It will be also interesting for biologist, doctoral students and medical residents interested in "Tumor Immunology".

Autorentext
Prof. Federico Garrido is Professor of Immunology at the University of Granada Medical School and head of the Dept. of Clinical Analysis & Immunology at the Hospital Universitario Virgen de las Nieves, Granada, Spain. After obtaining his MD and PhD degrees from the University of Granada in 1974, Prof. Garrido went on as a postdoctoral fellow at the laboratory of Dr. Hilliard Festenstein at the London Hospital Medical College in London, investigating the immunogenetics of the MHC (H-2) system by typing mouse tumour cells for H-2 expression. After returning to Granada in 1981 he continued his research on HLA typing of human tumour tissues. Prof. Garridos research focuses on the expression of HLA antigens in tumours and the role that these molecules play on tumour evasion from the immune system.

Zusammenfassung

This book is about the escape strategies used by cancer cells to avoid the immune response of the host. The main characters of this story are the Antigen Presenting Molecules and the T Lymphocytes. The former are known as the Major Histocompatibility Complex (MHC): the H-2 and the HLA molecules. The latter are a subgroup of white cells travelling all over our body which are capable to distinguish between self and non self.

Readers will know from the inside about the history of the HLA genetic system and will discover how T lymphocytes recognize and destroy cancer cells. One of the key important questions is: Why tumors arise, develop and metastasize? This book tries to answer this question and will explain how cancer cells become invisible to killer T lymphocytes. The loss of the HLA molecules is a major player in this tumor escape mechanism.

Cancer immunotherapy is aimed at stimulating T lymphocytes to destroy tumor cells. However, the clinical response rate is not as high as expected. The molecular mechanisms responsible for MHC/HLA antigen loss play a crucial role in this resistance to immunotherapy. This immune escape mechanism will be discussed in different types of tumors: lung, prostate, bladder and breastect. as well as melanoma and lymphoma.

This book will be useful to Oncologists, Pathologists and Immunologist that will enter this fascinating area of research. It will be also interesting for biologist, doctoral students and medical residents interested in Tumor Immunology.

Inhalt
Introduction I.- MHC/HLA class I loss in Primary Tumours

1-1. MHC-I heterogeneity in primary mouse sarcomas

1-2. HLA-I Heterogeneity in primary human tumours

1.3 Altered HLA-I tumour phenotypes

1-4 Molecular mechanisms underlying HLA-I altered expression

1-5 Reversible soft and irreversible hard molecular HLA-I lesions

1-6 T-cell immune selection of HLA-I negative tumour variants

1-7 HLA-I expression in different tumour tissues: melanoma, colorectal,

cervix, bladder, breast, gastric, head and neck, lung, pancreas, prostate

and thyroid carcinomas

1-8 An exception to the rule: HLA-I expression in renal cell carcinoma

1-9 An exception to the rule: T cell infiltration in MSI-H, HLA-I negative colorectal carcinoma

II.- MHC/HLA class I loss in metastases

2-1 H-2 class I expression in spontaneous metastases in mice

2-2 HLA class I expression in human metastases

2-3 HLA-I expression in progressing and regressing metastases after

immunotherapy

III.- Recovery of HLA-I antigen expression in cancer cells: a

challenge for the future

IV.- HLA- class II expression in human tumors

Concluding remarks