An Investigation into the potential Th17 phenotype of ALCL (360G-Wellcome-207192_Z_17_Z)

Anaplastic Large Cell Lymphoma (ALCL) is a paediatric T cell lymphoma whereby tumours have an 'activated' cell surface protein expression phenotype, defined by the presence of CD30. However, it has long been an enigma as to why these supposed ‘transformed T cells’ do not express a T cell receptor (TCR) despite having the capacity to do so (as evidenced by the presence of molecular rearrangements of VDJ genes). The presumed cell of origin is a cytotoxic T cell as the large majority of tumours produce perforin and granzyme B yet in many cases expression of the helper T cell protein CD4 is also observed. We have refined the tumour cell phenotype to show expression of RORgt and production of cytokines including IL26, IL22 and IL17 hence suggestive of an origin in an innate lymphoid 3 cell (perhaps when the TCR is 'missing') or Th17 cells (when the TCR is expressed) that develop into tumours as a consequence of an inflammatory environment. Hence, the aim of this project is to establish this cellular phenotype and define the role of the (sometimes missing) TCR.