T-Cells Present in Tumour Tissue May Affect the Outcome of Follicular Lymphoma.
Authors: Wahlin Björn E. , Kimby Eva , Sander Birgitta , Christensson Birger 
Published: October 2019

Abstract
Follicular lymphoma (FL) is characterized by a highly variable clinical course, with survival after diagnosis ranging from less than one year, to more than 20 years. The prognosis for the individual patient is difficult to assess. Sporadic reports have suggested that a high number of T-cells in FL lymph nodes may cause spontaneous regression of the lymphoma. To gain more knowledge of the prognostic importance of T-cells, a flow cytometric analysis of FL biopsy samples was performed. A total of 231 patients diagnosed with FL between 1 January 1994 and 31 December 2003 were identified in the pathology archives at Karolinska University Hospital, Huddinge. 121 of these patients had been diagnosed at the Department of Hematology, and for 87 patients out of the 121, complete data have been found, including clinical data from patient files and complete flow cytometric assays on diagnostic FL lymph nodes. The flow cytometry T- and B-cell markers included CD3, CD4, CD8, CD16/56, CD20, CD19 and CD25. The median age at diagnosis was 58.9 years (range 34.9—87.6 years). The median follow-up after FL diagnosis was 4.3 years (range 0.6—10.5 years). 49.4% of the patients were male. The patients received a variety of standard treatments. Information on disease stage was available for all 87 patients: stage I 15%, stage II 20%, stage III 22% and stage IV 44%. The histopathological diagnoses of the lymph nodes were FL grade 1 or grade 2 in 84% of the cases, and FL grade 3 in 16%. LDH-values were available for 98% of the patients. Median number of lymphocyte T- and NK-cell subsets in the lymph nodes were: CD3+: 29% (range 4—83%), CD4+CD3+: 22% (2—69%), CD8+CD3+: 6% (2—26%), CD25+CD3+: 6% (1—31%) and CD56+ and/or CD16+: 1% (0—2%). The CD4/CD8 ratio had a median of 3.6 (0.7—15). The median number of total B-cells was 69% (15—94%), and the median number of clonal B-cells was 65% (13—94%). Only cells within flow cytometric lymphocyte gate have been counted. For statistical grouping, the patients were divided by median values from the flow cytometry results. Kaplan-Meier analyses of the preliminary data have been performed. Comparison has been made, for each CD, between the group with higher-than-median counts and the group with median-and-lower counts. It seems that patients with a high CD3+ count might have a prolonged overall survival and event-free survival, compared to the patients with low CD3+ numbers. The group with high counts of activated (CD25+) T-cells showed a significantly better overall survival (p<0.01), compared to the group with low counts, but no difference was seen regarding event-free survival. Patients with FL lymph nodes containing more than the median of CD8+ cells, had a significantly prolonged event-free survival, compared to those with lower counts (p<0.05), and the same tendency could be seen for overall survival (p=0.12). Moreover, high counts of CD25+ and CD8+ cells were associated with low stage: among the patients with a high number of CD25+ cells, only 30% had stage IV disease, whereas in patient with low numbers, 60% had stage IV. The corresponding figures for patients with high and low CD8+ counts were 31% and 54%, respectively. There was no difference in LDH values between the high and low groups of CD25+ or CD8+. Differences in CD4+ counts or CD4/CD8 ratio did not seem to be of prognostic value. The study demonstrates that evaluation of different T-cell subsets in FL lymph nodes may be of value for predicting clinical course.