Our group has a long-standing interest in T cell responses against oncogenic human papillomaviruses (1-6).
We developed techniques to detect weak T cell responses against HPV, define CD8 and CD4 epitopes and to isolate T cell clones capable of killing cervical cancer cells.
Research
T cell responses against viral and tumour associated antigens
We test T cell responses in a phase I clinical trial of an HPV vaccine in oropharyngeal cancer patients.
More recently the laboratory has been involved in the definition of novel T cell antigens. This is based on the concept that aberrant proteasomal degradation of key regulatory proteins induced by viral infection/transformation will generate novel epitopes. We demonstrated that the pro-apoptotic protein Bax can be presented by this pathway in cancer cells (7).
Another interest of the group is the definition of immune signatures based on immune cell phenotype and function, as prognostic markers.
We have recently shown that abnormal expansion of CD8 T subsets in chronic lymphocytic leukaemia (CLL) results in an inverted CD4:CD8 ratio, and correlates with poorer clinical prognosis (8).
We will be investigating the antigen specificity and function of these CD8 T cells, in particular examining the influence of persistent viruses such as HCMV.
Cyhoeddiadau
- Nunes, C. T. et al. 2012. Expansion of a CD8+PD-1+ replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clinical Cancer Research 18 (3), pp.678-687. (10.1158/1078-0432.CCR-11-2630)
- Nunes, C. T. et al. 2011. A novel tumor antigen derived from enhanced degradation of Bax protein in human cancers. Cancer Research 71 (16), pp.5435-5444. (10.1158/0008-5472.CAN-11-0393)
- Campo, M. S. et al., 2010. HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology 407 (1), pp.137-142. (10.1016/j.virol.2010.07.044)
- Chan, P. K. S. et al., 2010. T-Cell response to human papillomavirus type 58 L1, E6, and E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer. Clinical and Vaccine Immunology 17 (9), pp.1315-1321. (10.1128/CVI.00105-10)
- Smith, K. L. et al., 2005. Epitope specificity and longevity of a vaccine-induced human T cell response against HPV18. International Immunology 17 (2), pp.167-176. (10.1093/intimm/dxh197)
- Evans, M. et al. 2001. Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6. The Journal of Immunology 167 (9), pp.5420-5428.
- Nimako, M. et al., 1997. Human papillomavirus-specific cytotoxic T lymphocytes in patients with cervical intraepithelial neoplasia grade III. Cancer Research 57 (21), pp.4855-4861.
Ysgolion
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