AUTHOR=Wu Xun , Fajardo-Despaigne J. Ernesto , Zhang Christine , Neppalli Vishala , Banerji Versha , Johnston James B. , Gibson Spencer B. , Marshall Aaron J. 

TITLE=Altered T Follicular Helper Cell Subsets and Function in Chronic Lymphocytic Leukemia

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.674492

DOI=10.3389/fonc.2021.674492

ISSN=2234-943X

ABSTRACT=<p>Follicular helper T cells (T<sub>FH</sub>) have specialized properties in promoting normal B cell activation but their role in chronic lymphocytic leukemia (CLL) is unknown. We find that T<sub>FH</sub> cells are elevated in CLL patients and are phenotypically abnormal, expressing higher levels of PD-1, TIGIT, CD40L, IFNγ and IL-21, and exhibiting abnormal composition of T<sub>FH</sub>1, T<sub>FH</sub>2 and T<sub>FH</sub>17 subsets. Frequencies of CD4-positive T cells expressing T<sub>FH</sub>1 markers and IL-21 were positively correlated with patient lymphocyte counts and RAI stage, suggesting that accumulation of abnormal T<sub>FH</sub> cells is concomitant with expansion of the leukemic B cell clone. Treatment with ibrutinib led to normalization of T<sub>FH</sub> frequencies and phenotype. T<sub>FH</sub> cells identified in CLL bone marrow display elevated expression of several functional markers compared to blood T<sub>FH</sub> cells. CLL T cell-B cell co-culture experiments revealed a correlation of patient T<sub>FH</sub> frequencies with functional ability of their CD4-positive T cells to promote CLL proliferation. Conversely, CLL cells can preferentially activate the T<sub>FH</sub> cell subset in co-culture. Together our results indicate that CLL development is associated with expansion of abnormal T<sub>FH</sub> populations that produce elevated levels of cytokines and costimulatory molecules which may help support CLL proliferation.</p>