12-06-2013, 09:01 PM
A new study from researchers in the Fred Hutchinson Cancer Research Center, Seattle, USA and the University of Washington, Seattle has developed a DNA-based assay, in order to reliably count tumour-infiltrating lymphocytes (TILs) and asses their T cell clonality. This should help with use of TILs as a reliable prognostic biomarker in cancer. The study, published this week in the journal Science Translational Medicine addresses technical issues that have previously made quantification of TILs and scoring of their presence in tumours difficult and inconsistent.
It is generally agreed that TIL infiltration is correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). EOC is one of the most deadly gynaecological tumours and prognosis based on clinicopathological features is difficult. A previous study used deep sequencing of rearranged T-cell receptor beta (TCRB) genes to characterise TILs in ovarian carcinoma. It was shown that the TIL repertoires are similar throughout ovarian carcinomas but distinct from the repertoire in circulating T cells. That study concluded that there was a distinct cellular adaptive immune response within ovarian carcinomas mediated by TILs. Autoantibodies are another form of defence against EOC and a study showed that autoantibodies to the common tumour antigen NY-ESO-1 correlates with TILs in solid tumour and ascites in tissue samples from high-grade serous ovarian cancer. This suggests that TILs and autoantibodies may cooperate in a host cancer immune response against tumour antigens.
In the current Science Translational Medicine study, the authors addressed the problem of limited inclusion of TILs in standard prognostic panels due to difficulties in reliably counting them and lack of consistent criteria in scoring TILs across studies. The study introduced a robust digital DNA-based assay, termed QuanTILfy, to count TILs and assess T cell clonality in tissue samples, including tumours. The researchers used tumour samples from 30 ovarian cancer patients whose survival outcomes were known and were able to make accurate, sensitive, and highly reproducible measurement of TILs in both primary and metastatic ovarian cancer. They confirmed that there was a direct relationship between higher TIL counts and improved survival among women with ovarian cancer. They observed that, surprisingly, the TIL repertoire was diverse for all tumours in the study.
The authors conclude that the development of a sensitive, standardisable and reproducible DNA-based assay such as their QuanTILfy should enable TILs to be used a prognostic indicator in a range of cancer types including ovarian cancer. This should in turn help in decisions about patient care and treatment.
Sources
ROBINS, S., ERICSON, N. G., GUENTHOER, J., O’BRIANT, K. C. , TEWARI, M., DRESCHER, C. W. and BIELAS, J. H., 2013. Digital Genomic Quantification of Tumor-Infiltrating Lymphocytes. Sci. Transl. Med. 5, 214ra169 (2013).
BACHMAYR-HEYDA, A., AUST, S., HEINZE, G., POLTERAUER, S., GRIMM, C., BRAICU, E.I., SEHOULI, J., LAMBRECHTS, S., VERGOTE, I., MAHNER, S., PILS, D., SCHUSTER, E., THALHAMMER, T., HORVAT, R., DENKERT, C., ZEILLINGER, R. and CASTILLO-TONG, D., 2013. Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients - a study of the OVCAD consortium. BMC Cancer, 13, pp. 422-422.
EMERSON, R.O., SHERWOOD, A.M., RIEDER, M.J., GUENTHOER, J., WILLIAMSON, D.W., CARLSON, C.S., DRESCHER, C.W., TEWARI, M., BIELAS, J.H. and ROBINS, H.S., 2013. High-throughput sequencing of T cell receptors reveals a homogeneous repertoire of tumor-infiltrating lymphocytes in ovarian cancer. The Journal of Pathology, 2013.
MILNE, K., BARNES, R.O., GIRARDIN, A., MAWER, M.A., NESSLINGER, N.J., NG, A., NIELSEN, J.S., SAHOTA, R., TRAN, E., WEBB, J.R., WONG, M.Q., WICK, D.A., WRAY, A., MCMURTRIE, E., KöBEL, M., KALLOGER, S.E., GILKS, C.B., WATSON, P.H. and NELSON, B.H., 2008. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer. Plos One, 3(10), pp. e3409-e3409.
Fred Hutchinson Cancer Research Center. "Predicting ovarian cancer survival by counting tumor-attacking immune cells." ScienceDaily, 4 Dec. 2013. [Accessed 6 Dec. 2013].
It is generally agreed that TIL infiltration is correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). EOC is one of the most deadly gynaecological tumours and prognosis based on clinicopathological features is difficult. A previous study used deep sequencing of rearranged T-cell receptor beta (TCRB) genes to characterise TILs in ovarian carcinoma. It was shown that the TIL repertoires are similar throughout ovarian carcinomas but distinct from the repertoire in circulating T cells. That study concluded that there was a distinct cellular adaptive immune response within ovarian carcinomas mediated by TILs. Autoantibodies are another form of defence against EOC and a study showed that autoantibodies to the common tumour antigen NY-ESO-1 correlates with TILs in solid tumour and ascites in tissue samples from high-grade serous ovarian cancer. This suggests that TILs and autoantibodies may cooperate in a host cancer immune response against tumour antigens.
In the current Science Translational Medicine study, the authors addressed the problem of limited inclusion of TILs in standard prognostic panels due to difficulties in reliably counting them and lack of consistent criteria in scoring TILs across studies. The study introduced a robust digital DNA-based assay, termed QuanTILfy, to count TILs and assess T cell clonality in tissue samples, including tumours. The researchers used tumour samples from 30 ovarian cancer patients whose survival outcomes were known and were able to make accurate, sensitive, and highly reproducible measurement of TILs in both primary and metastatic ovarian cancer. They confirmed that there was a direct relationship between higher TIL counts and improved survival among women with ovarian cancer. They observed that, surprisingly, the TIL repertoire was diverse for all tumours in the study.
The authors conclude that the development of a sensitive, standardisable and reproducible DNA-based assay such as their QuanTILfy should enable TILs to be used a prognostic indicator in a range of cancer types including ovarian cancer. This should in turn help in decisions about patient care and treatment.
Sources
ROBINS, S., ERICSON, N. G., GUENTHOER, J., O’BRIANT, K. C. , TEWARI, M., DRESCHER, C. W. and BIELAS, J. H., 2013. Digital Genomic Quantification of Tumor-Infiltrating Lymphocytes. Sci. Transl. Med. 5, 214ra169 (2013).
BACHMAYR-HEYDA, A., AUST, S., HEINZE, G., POLTERAUER, S., GRIMM, C., BRAICU, E.I., SEHOULI, J., LAMBRECHTS, S., VERGOTE, I., MAHNER, S., PILS, D., SCHUSTER, E., THALHAMMER, T., HORVAT, R., DENKERT, C., ZEILLINGER, R. and CASTILLO-TONG, D., 2013. Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients - a study of the OVCAD consortium. BMC Cancer, 13, pp. 422-422.
EMERSON, R.O., SHERWOOD, A.M., RIEDER, M.J., GUENTHOER, J., WILLIAMSON, D.W., CARLSON, C.S., DRESCHER, C.W., TEWARI, M., BIELAS, J.H. and ROBINS, H.S., 2013. High-throughput sequencing of T cell receptors reveals a homogeneous repertoire of tumor-infiltrating lymphocytes in ovarian cancer. The Journal of Pathology, 2013.
MILNE, K., BARNES, R.O., GIRARDIN, A., MAWER, M.A., NESSLINGER, N.J., NG, A., NIELSEN, J.S., SAHOTA, R., TRAN, E., WEBB, J.R., WONG, M.Q., WICK, D.A., WRAY, A., MCMURTRIE, E., KöBEL, M., KALLOGER, S.E., GILKS, C.B., WATSON, P.H. and NELSON, B.H., 2008. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer. Plos One, 3(10), pp. e3409-e3409.
Fred Hutchinson Cancer Research Center. "Predicting ovarian cancer survival by counting tumor-attacking immune cells." ScienceDaily, 4 Dec. 2013. [Accessed 6 Dec. 2013].
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