Tumor-infiltrating cells as a prognostic factor in Hodgkin's lymphoma:: A quantitative tissue microarray study in a large retrospective cohort of 267 patients

The present study aimed to describe the general tissular composition of the immune infiltrate observed in Hodgkin's lymphoma (HL) and its possible relationship with clinical and survival prognostic factors. In this retrospective study of 267 HL patients, the relative proportions of infiltrating T lymphocytes (CD4(+), CD8(+)), natural killer cells (CD56(+), CD57(+)), cytotoxic cells (Granzyme B+, TIA-1+) and dendritic cells (CD21+, S-100+) were quantified immunohistochemically with tissue microarray technology. Our results confirm the predominance of CD4+ T lymphocytes in the background of tumoral cells, in addition to a high number of cytotoxic lymphocytes (CD8, CD57 and TIA-1). Patients with low numbers of infiltrating CD8, CD56, CD57+ cells and high numbers of Granzyme B and TIA-1+ cells presented a significantly unfavourable clinical course (presence of leukocytosis, B symptoms, advanced clinical stage (III/IV), non-responding patients). A reduced infiltration of CD4+ T lymphocytes was related with the presence of Epstein-Barr virus. Significantly longer survival times were observed in patients with a high level of infiltrating CD57, as well as a low level of Granzyme B and TIA-1+ cells (log-rank test). When evaluated in a multivariate model, high levels of infiltrating TIA- 1 and Granzyme B+ cells were shown to be independent prognostic factors that negatively influenced overall survival. The presence of TIA-1+ cells was found to be the only unfavorable prognostic factor of event-free survival and disease-free survival. The overall detection of tumor-infiltrating cells in HL confirms the importance of cytotoxic T lymphocyte infiltration (Granzyme B and TIA-1+ cells) in these patients. Independently of the classical clinical and pathological features, these cells appear to be an unfavourable prognostic factor in HL and, more particularly, the presence of cytotoxic TIA-1+ cells.