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Jennifer R. Brown, MD, PhD


Complementary Strategies to Manage CLL: Focus on Restoring Immune Function

By: Victoria Kuhr, BA
Posted: Thursday, January 27, 2022

The interaction of leukemic cells with T cells and other players of the immune system appears to participate in the pathogenesis of chronic lymphocytic leukemia (CLL) and may contribute to a decrease in patients’ overall health status, according to researchers in Spain. Additionally, José-Ángel Hernández-Rivas, MD, PhD, of Hospital Universitario Infanta Leonor, Madrid, and colleagues proposed that both T and B cells can create a protumor environment that may restore immune function in this patient population.

“There is growing evidence that T cells play a very relevant role in disease progression, and understanding how T and B cells create a protumor environment is essential to treat CLL patients,” said the researchers.

The study reviews the current understanding of the interplay between malignant cells and non-malignant immune cells, which may promote tumor survival and proliferation. In addition, the study authors review the available evidence on how different treatment options for CLL (eg, chemoimmunotherapies, small-molecule inhibitors, and T-cell therapies) affect the immune system and their clinical consequences.

Specifically, two immunotherapies in combination, ibrutinib and venetoclax, have been reported to reduce tumor prosurvival cells, and ibrutinib has enhanced venetoclax killing effects by sensitizing CLL B cells to the BCL2 antagonism of venetoclax. Additionally, studies combining venetoclax and obinutuzumab have shown a decrease not only in CLL B cells, but also in healthy B, T, and NK cells. In addition, this combination generates a decrease in IFN-γ and TNF-α produced by CD8-positive T cells.

“New insights [in CLL] have shown that the interaction of leukemic cells with T cells and other players of the immune system participate in the pathogenesis of the disease and contribute to a decrease of the overall health status of the patient, but this knowledge has not fully been applied to clinical practice yet,” the study authors commented.

Disclosure: For full disclosures of the study authors, visit

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