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Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia.

ABSTRACT: Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of mature CD19⁺CD5⁺CD23⁺ B cells in the bloodstream and in lymphoid organs. It usually affects people over 70 years of age, which limits the options for treatments. The disease is typically well-managed, but to date is still incurable. Hence, the need for novel therapeutic strategies remains. Nurse-like cells (NLCs) are major components of the microenvironment for CLL, supporting tumor cell survival, proliferation, and even drug resistance. They are of myeloid lineage, guided toward differentiating into their tumor-supportive role by the CLL cells themselves. As such, they are analogous to tumor-associated macrophages and represent a major therapeutic target. Previously, it was found that a mushroom extract, Active Hexose-Correlated Compound (AHCC), promoted the death of acute myeloid leukemia cells while preserving normal monocytes. Given these findings, it was asked whether AHCC might have a similar effect on the abnormally differentiated myeloid-lineage NLCs in CLL. CLL-patient PBMCs were treated with AHCC, and it was found that AHCC treatment showed a direct toxic effect against isolated CLL cells. In addition, it significantly reduced the number of tumor-supportive NLCs and altered their phenotype. The effects of AHCC were then tested in the Eµ-TCL1 mouse model of CLL and the Mll^PTD/WT Flt3^ITD/WT model of AML. Results showed that AHCC not only reduced tumor load and increased survival in the CLL and AML models, but it also enhanced antitumor antibody treatment in the CLL model. These results suggest that AHCC has direct and indirect effects against CLL and that it may be of benefit when combined with existing treatments.

SUBMITTER: Merchand-Reyes G

PROVIDER: S-EPMC10747249 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia.

Merchand-Reyes Giovanna G Santhanam Ramasamy R Valencia-Pena Maria L ML Kumar Krishan K Mo Xiaokui X Belay Tesfaye T Woyach Jennifer A JA Mundy-Bosse Bethany B Tridandapani Susheela S Butchar Jonathan P JP

Nutrients 20231218 24

Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of mature CD19+CD5+CD23+ B cells in the bloodstream and in lymphoid organs. It usually affects people over 70 years of age, which limits the options for treatments. The disease is typically well-managed, but to date is still incurable. Hence, the need for novel therapeutic strategies remains. Nurse-like cells (NLCs) are major components of the microenvironment for CLL, supporting tu ...[more]

PMID: 38140397

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Project description:The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment through several cross-talk mechanisms. In this review, we describe how chronic lymphocytic leukemia cells participate in this interplay by inducing migration and tumor-supportive differentiation of bystander cells. Furthermore, chronic lymphocytic leukemia-mediated alterations in the interactions between bystander cells are discussed. Upon bystander cell interaction, chronic lymphocytic leukemia cells secrete cytokines and chemokines such as migratory factors [chemokine (C-C motif) ligand 22 and chemokine (CC motif) ligand 2], which result in further recruitment of T cells but also of monocyte-derived cells. Within the tumor microenvironment, chronic lymphocytic leukemia cells induce differentiation towards a tumor-supportive M2 phenotype of monocyte-derived cells and suppress phagocytosis, but also induce increased numbers of supportive regulatory T cells. Like other tumor types, the differentiation of stromal cells towards supportive cancer-associated fibroblasts is critically dependent on chronic lymphocytic leukemia-derived factors such as exosomes and platelet-derived growth factor. Lastly, both chronic lymphocytic leukemia and bystander cells induce a tolerogenic tumor microenvironment; chronic lymphocytic leukemia-secreted cytokines, such as interleukin-10, suppress cytotoxic T-cell functions, while chronic lymphocytic leukemia-associated monocyte-derived cells contribute to suppression of T-cell function by producing the immune checkpoint factor, programmed cell death-ligand 1. Deeper understanding of the active involvement and cross-talk of chronic lymphocytic leukemia cells in shaping the tumor microenvironment may offer novel clues for designing therapeutic strategies.

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Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia.

Publications

Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia.

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