Increased expression of costimulatory molecules CD86 and sCTLA-4 in patients with acute lymphoblastic leukemia

Mansour, Amany H.; Elkhodary, Tawf i k; Darwish, Ahmad; Mabed, Mohamed

doi:10.3109/10428194.2013.869328

Cited by 22 publications

(22 citation statements)

References 28 publications

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“…Interestingly, despite these changes, end-of-induction MRD assessment is still reliable, due to our ability to identify a IP-aberrant population (whether identical, or slightly different from the B-ALL diagnostic IP) from normal B-cell precursors with a characteristic FCM pattern of maturation. Other markers such as CD86, CD49f, and CD304 may be potentially useful for MRD detection (33)(34)(35)(36)(37). Loss of CD19 is seen in 10-20% of patients post CAR-T, is associated with relapse, and is due to mutation and/or alternative splicing of the CD19 gene (32).…”

Section: Discussionmentioning

confidence: 99%

Early recovery of circulating immature B cells in B‐lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection

Xiao

Salem

McCoy

et al. 2017

Cytometry Part B Clinical

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These circulating CD10 + B-cells are compatible with immature B-cells, and are a reflection of B-cell recovery within the marrow. They are immunophenotypically distinguishable from residual B-ALL. Expression of light chain sIg and key surface antigens characterizing regenerating B-cell precursors can distinguish immature B-cells from B-ALL MRD and prevent misdiagnosis. © 2017 International Clinical Cytometry Society.

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Section: Discussionmentioning

confidence: 99%

Early recovery of circulating immature B cells in B‐lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection

Xiao

Salem

McCoy

et al. 2017

Cytometry Part B Clinical

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“…Functional blocking of sCTLA‐4 had a protective effect in melanoma in mice . In a huge majority of pediatric patients of B‐cell acute lymphoblastic leukemia (B‐ALL) with active disease, sCTLA‐4 was found to be upregulated, which correlated positively with the frequency of leukemic B cells in the patients . Investigation of sera of patients with breast cancer also revealed significantly increased sCTLA‐4 levels as compared with age‐ and sex‐matched healthy controls .…”

Section: Immune Checkpoint Molecules: Regulating the Immune Response mentioning

confidence: 97%

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

2019

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Background With the recent advances in the understanding of the interaction of the immune system with developing tumor, it has become imperative to consider the immunological parameters for both cancer diagnosis and disease prognosis. Additionally, in the era of emerging immunotherapeutic strategies in cancer, it is very important to follow the treatment outcome and also to predict the correct immunotherapeutic strategy in individual patients. There being enormous heterogeneity among tumors at different sites or between primary and metastatic tumors in the same individual, or interpatient heterogeneity, it is very important to study the tumor‐immune interaction in the tumor microenvironment and beyond. Importantly, molecular tools and markers identified for such studies must be suitable for monitoring in a noninvasive manner. Recent findings Recent studies have shown that the immune checkpoint molecules play a key role in the development and progression of tumors. In‐depth studies of these molecules have led to the development of most of the cancer immunotherapeutic reagents that are currently either in clinical use or under different phases of clinical trials. Interestingly, many of these cell surface molecules undergo alternative splicing to produce soluble isoforms, which can be tracked in the serum of patients. Conclusions Several studies demonstrate that the serum levels of these soluble isoforms could be used as noninvasive markers for cancer diagnosis and disease prognosis or to predict patient response to specific therapeutic strategies.

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“…Besides membrane-bound CTLA-4, a native soluble form of CTLA-4 (sCTLA-4), produced by alternative CTLA-4 mRNA splicing, has been described for a variety of autoimmune diseases and may play a role in regulating immune responses [86]. Significantly elevated levels of circulating sCTLA-4 also have been reported in pediatric patients with B-ALL and were associated with a poor prognosis [87, 88]. …”

Section: Emerging Role Of Immune Checkpoints In Immune Escape By Amentioning

confidence: 99%

Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

Knaus¹,

Kanakry²,

Luznik³

et al. 2017

CDT

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Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body’s own immune system to fight leukemic cells.

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Increased expression of costimulatory molecules CD86 and sCTLA-4 in patients with acute lymphoblastic leukemia

Cited by 22 publications

References 28 publications

Early recovery of circulating immature B cells in B‐lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection

Early recovery of circulating immature B cells in B‐lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

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