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Characterization of human prostate and breast cancer cell lines for experimental T cell-based immunotherapy
Björn Carlsson1, Ole Forsberg, Mats Bengtsson
1Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Background:
In order to develop experimental immunotherapy for prostate and breast cancer it is of outmost importance to have representative target cell lines that through human leukocyte antigen (HLA) class I molecules present relevant levels of peptides from tumor-associated antigens for cytotoxic T lymphocyte (CTL) recognition.
Methods:
We sequenced the HLA-A and HLA-B loci of eight commonly used prostate and breast cancer cell lines and analyzed the surface expression of HLA-ABC, HLA-DR, CD40, CD80, CD86, and CD54 by flow cytometry. We also analyzed the cell lines for mRNA expression from 25 genes reported to be specifically or preferentially expressed by prostate cells.
Results:
Among the analyzed cell lines we found that LNCaP, PC-346C and MCF-7 are HLA-A*0201 positive. However, the HLA-A2 expression level is low and only MCF-7 upregulates HLA-A2 in response to IFN-gamma stimulation. MCF-7 also expresses high levels of CD54, which further improve its value as a CTL target cell line. On the other hand, LNCaP and PC-346C express 25 and 23 out of 25 prostate-related genes, respectively, while MCF-7 expresses 16 out of 25 genes.
Conclusions:
None of the analyzed prostate cancer cell lines are optimal CTL target cells. However, MCF-7 could in many cases be used as a complement to HLA-A*0201 positive prostate cancer cells. The LNCaP and PC-346C cell lines are rich sources of prostate-related antigens that may be valuable for cancer vaccine development.
Insights
No ideal prostate cancer cell lines were found for immunotherapy. However, MCF-7 breast cancer cells can complement HLA-A*0201 positive prostate cells, and LNCaP/PC-346C cells are valuable for prostate cancer vaccine development.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Developing effective cancer immunotherapies requires representative target cell lines.
- These cell lines must present tumor-associated antigens via human leukocyte antigen (HLA) class I molecules for cytotoxic T lymphocyte (CTL) recognition.
Purpose of the Study:
- To evaluate commonly used prostate and breast cancer cell lines as targets for immunotherapy.
- To assess their suitability for cytotoxic T lymphocyte (CTL) recognition by analyzing HLA expression and tumor-associated antigen presentation.
Main Methods:
- Sequencing of HLA-A and HLA-B loci in eight cancer cell lines.
- Flow cytometry analysis of surface expression for HLA-ABC, HLA-DR, CD40, CD80, CD86, and CD54.
- mRNA expression analysis of 25 prostate-specific genes.
Main Results:
- LNCaP, PC-346C, and MCF-7 cells are positive for HLA-A*0201, but HLA-A2 expression is low, with only MCF-7 upregulating it upon IFN-gamma stimulation.
- MCF-7 exhibits high CD54 expression, enhancing its utility as a CTL target.
- LNCaP and PC-346C express a high number of prostate-related genes (25 and 23, respectively), while MCF-7 expresses 16.
Conclusions:
- No single prostate cancer cell line is optimal for CTL-based immunotherapy.
- MCF-7 can serve as a valuable complement to HLA-A*0201 positive prostate cancer cells.
- LNCaP and PC-346C cell lines are rich sources of prostate antigens, beneficial for cancer vaccine development.
