Increased CD68, Decreased CD4 Associated with Poor Outcome in CLL

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2781] Increased CD68 and Decreased CD4 Expressing Cells in Tissue

Microarray (TMA) in Diagnostic Lymph Node Biopsies Are Associated

with Poor Outcome in CLL/SLL. Session Type: Poster Session, Board

#10-III

Abigail M. Lee, Clear, Calaminici, Finlay Macdougall,

Lindsey Goff, G. Gribben CRUK Medical Oncology, Barts and The

London School of Medicine, London, United Kingdom; Histopathology,

Barts and The London NHS Trust, London, United Kingdom

Increasing evidence supports the importance of the number and

location of tumor infiltrating lymphocytes (TILs) in cancer.

Although increased circulating T regulatory cells have been found in

CLL, no reports to date have examined the nature of the immune

microenvironment in the lymph node (LN) in CLL/SLL. We therefore

constructed TMAs composed of 1mm cores from initial diagnostic lymph

nodes in 35 patients with CLL/SLL.

The diagnosis of CLL/SLL was confirmed in all cases. The goals of

the study were 1) to examine the nature of TILs in this disease, 2)

to compare any changes in protein expression with those we have

identified by gene expression profiling in peripheral blood T cells,

3) to examine the immune microenvironment in those cases with and

without a leukemic component, ie comparing SLL with CLL, and 4) to

assess the ability to discriminate prognostic groups based upon

immunohistochemistry of diagnostic lymph nodes.

The first group of 17 patients were selected on the basis of poor

outcome, with median survival of 38 months from diagnosis, with all

patients dying of their disease. The median age of this group at

presentation was 62 years, 12 were male and 5 female. The second

group of 18 patients were selected on the basis of long survival and

had median survival of more than 10 years. Their median age at

presentation was 53 years, 11 were male and 7 female.

Immunohistochemistry was performed on the TMAs using a panel of

monoclonal antibodies including CD4, CD8, CD25, CD6, CD7, FOXP3,

CD68, TIA-1 and Granzyme B. The immune infiltrates were scored based

on immunophenotype, frequency and location. All cores were analyzed

independently by two histopathologists and concordance was achieved

in all cases. The majority of cases in both groups had >30 CD8

expressing cells per high power field (hpf) as well as a high

frequency of FOXP3 expressing cells, whereas we observed low number

of cells expressing TIA-1 and granzyme B.

In keeping with our previous gene expression profiling data in

peripheral blood T cells, CD6 was expressed in a lower frequency of

cells in the poor prognosis group. The poor prognosis group also had

fewer CD4 but increased CD25 expressing T cells, as well as

increased CD68 expressing monocytes. Ongoing studies are assessing

the use of TMA in LN and bone marrow biopsies in CLL/SLL in a larger

cohort of patients as well as analyzing additional antibodies,

particularly for those antigens previously identified by gene

expression profiling.

The results are in keeping with the hypothesis that there is a

complex interaction between the disease and the immune

microenvironment in the LN in CLL/SLL and that the immune

microenvironment represents a rational therapeutic target in this

disease.