Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks

Abstract

The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells. High CLL counts were associated with low activation on circulating monocytes and T cells and vice versa. The highest activation of immune cells, particularly of intermediate and non-classical monocytes, was evident in patients treated with novel agents. PSNs revealed a low activation of immune cells in CLL progression, irrespective of IgHV status, Binet stage and TP53 disruption. Patients with high intermediate monocytes (> 5.4%) with low activation were 2.5 times more likely (95% confidence interval 1.421–4.403, P = 0.002) to had shorter time-to-treatment than those with low monocyte counts. Our study demonstrated the association between the activation of circulating immune cells and the bulk of CLL cells. The highest activation of bystander immune cells was detected in patients with slow disease course and in those treated with novel agents. The subset of intermediate monocytes showed predictive value for time-to-treatment in CLL.

Network Analysis for Uncovering the Relationship between Host Response and Clinical Factors to Virus Pathogen: Lessons from SARS-CoV-2

“…Among immunological factors, the main immune cell populations and subpopulations and their activation in peripheral blood were determined using flow cytometry. Whole blood samples were prepared for eight-colour flow cytometry as previously described [19]. Isotype-matched conjugated irrelevant antibodies and fluorescence minus one controls were used.…”

miR-155 and miR-223 as markers of biological and clinical features of chronic lymphocytic leukemia

“…Хронический лимфолейкоз (ХЛЛ) -по международной классификации сhronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/ SLL) [4] -определяют как опухоль из малых В-лимфоцитов, характеризующуюся пролиферацией и накоплением аберрантных лимфоидных клеток в костном мозге, крови, лимфоидных тка-нях [5]. Хронический лимфолейкоз -неизлечимое злокачественное новообразование, на долю которого в западных странах приходится почти треть лейкозов и при котором наблюдается высокая межиндивидуальная клиническая и молекулярная гетерогенность [6][7][8]. Эта гетерогенность дополнительно усложняется изменением экспрессии генов и событиями эпигенетической регуляции, за которые отвечают регуляторные РНК, включая miR, выступающие в роли онкогенов либо супрессоров опухоли [9,10].…”

Reduced Absolute Count of Monocytes in Patients Carrying Hematological Neoplasms and SARS-CoV2 Infection

“…In multiple myeloma (MM), either anergic, dysfunctional effector lymphocytes or both, tumor-educated myeloid-derived suppressor cells and soluble mediators promote coordinately cancer immune-evasion [ 17 , 18 , 19 , 20 , 21 , 22 ]. In chronic lymphatic leukemia (CLL), circulating monocytes have a skewed aberrant phenotype leading to altered composition and phagocytosis, contributing T-cell exhaustion and anergy [ 23 , 24 , 25 , 26 ]. In Hodgkin’s lymphoma (HL) monocyte-like myeloid derived suppressor cells are increased and correlate to chemosensitivity [ 19 , 27 , 28 , 29 , 30 , 31 ].…”