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The cancer antigenome
Bianca Heemskerk1, Pia Kvistborg, Ton N M Schumacher
1Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
Cancer cells deviate from normal body cells in two immunologically important ways. First, tumour cells carry tens to hundreds of protein-changing mutations that are either responsible for cellular transformation or that have accumulated as mere passengers. Second, as a consequence of genetic and epigenetic alterations, tumour cells express a series of proteins that are normally not present or present at lower levels. These changes lead to the presentation of an altered repertoire of MHC class I-associated peptides. Importantly, while there is now strong clinical evidence that cytotoxic T-cell activity against such tumour-associated antigens can lead to cancer regression, at present we fail to understand which tumour-associated antigens form the prime targets in effective immunotherapies. Here, we describe how recent developments in cancer genomics will make it feasible to establish the repertoire of tumour-associated epitopes on a patient-specific basis. The elucidation of this 'cancer antigenome' will be valuable to reveal how clinically successful immunotherapies mediate their effect. Furthermore, the description of the cancer antigenome should form the basis of novel forms of personalized cancer immunotherapy.
Insights
Cancer cells have unique mutations and proteins, leading to altered immune peptide presentation. Understanding the cancer antigenome will guide personalized immunotherapies for effective cancer treatment.
Area of Science:
- Immunology
- Cancer Genomics
- Oncology
Background:
- Tumor cells exhibit distinct characteristics compared to normal cells, including numerous mutations and altered protein expression.
- These alterations result in a modified presentation of peptides associated with MHC class I molecules.
- Cytotoxic T-cell responses against tumor-associated antigens are clinically validated for cancer regression, yet target antigens remain poorly understood.
Purpose of the Study:
- To leverage recent advancements in cancer genomics.
- To enable the identification of tumor-associated epitopes on a patient-specific level.
- To establish the 'cancer antigenome' for understanding immunotherapy mechanisms and developing personalized treatments.
Main Methods:
- Analysis of cancer cell mutations and epigenetic alterations.
- Identification of tumor-specific protein expression.
- Characterization of altered MHC class I-associated peptide repertoires.
- Application of cancer genomics for epitope discovery.
Main Results:
- Feasibility of establishing patient-specific tumor-associated epitope repertoires.
- Potential to elucidate the mechanisms of successful cancer immunotherapies.
- Foundation for developing novel personalized cancer immunotherapy strategies.
Conclusions:
- The 'cancer antigenome' can be elucidated using current cancer genomics technologies.
- Understanding the cancer antigenome is crucial for deciphering how immunotherapies achieve cancer regression.
- Elucidation of the cancer antigenome will pave the way for personalized cancer immunotherapy.
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