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

Abstract

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 (CD 56+, CD 57+), cytotoxic cells (Granzyme B+, TIA-1+) and dendritic cells (CD 21+, 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, CD 57 and TIA-1). Patients with low numbers of infiltrating CD8, CD 56, CD 57+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 CD 57, 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.

Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome

“…Other IHC markers were specific for cell populations suspected to influence the molecular signature, such as CD20 for B cells and BDCA2 for plasmacytoid dendritic cells (pDCs). Other markers were reported to have prognostic value in cHL, such as BCL2, 15 FOXP-3, [19][20][21][22] TIA-1, 19,20 granzyme B, [19][20][21] STAT1, 20 and topo-II␣. 16 The remaining antibodies were markers of reactive cells that may interact with RS cells, such as tryptase (mast cells), PS100 (dendritic cells), CD8, CD57, and PD-1 (T-cell subsets).…”

“…18 Other IHC reports have highlighted the characteristics of nonmalignant immune cells that may predict unfavorable outcome, in particular a low infiltration of intratumoral FOXP3 ϩ Treg cells in combination with a high percentage of either granzyme B ϩ or TIA-1 ϩ lymphocytes. [19][20][21][22] In contrast to immunohistochemistry (IHC), gene expression profiling has been rarely used to analyze cHL tissues. A recent series of 23 cHL cases was focused on EBV-induced alterations.…”

Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in classical Hodgkin's lymphoma

“…2 Two components of the inflammatory background are associated with survival in classical Hodgkin's lymphoma: tumorinfiltrating lymphocytes 3,4 and a low lymphocyte count, which is defined by the IPS as less than 600 cells/mL or less than 8% of the white blood cell count and is a negative prognostic factor for survival in classical Hodgkin's lymphoma.…”

Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival

“…Despite the incorporation of several such parameters in a prognostic model, a sizeable fraction of high-risk patients still could not be identified in one study, 1 underscoring the need for better biomarkers. In this quest, several recent studies have focused on evaluating tissue-specific predictive biomarkers related either to the microenvironment of cHL [2][3][4][5][6][7] or to antigens expressed on the Hodgkin/Reed-Sternberg (HRS) cells [8][9][10] with variable success in identifying patients with poor outcomes, although they warrant validation in larger independent cohorts.…”