Role of LFA-1 and ICAM-1 in Cancer

B Cell ◽

Tumor Cells ◽

Human Body ◽

Detailed Examination ◽

Lymphocytic Leukemia ◽

Lymphocyte Function ◽

Tumor Growth And Metastasis ◽

The lymphocyte function–associated antigen-1 (LFA-1) (also CD11a/CD18 and alphaLbeta2), is just one of many integrins in the human body, but its significance derives from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1. A more detailed examination of LFA’s role within B-cell chronic lymphocytic leukemia is made. Finally, we discuss the role of LFA-1-harboring exosomes in tumor growth and metastasis.

Role of LFA-1 and ICAM-1 in Cancer

10.20944/preprints201709.0146.v2 ◽

2017 ◽

Author(s):

Manuel Reina ◽

Enric Espel

Keyword(s):

Tumor Cells ◽

Human Body ◽

Detailed Examination ◽

Lymphocytic Leukemia ◽

Lymphocyte Function ◽

Beta 2 ◽

Tumor Growth And Metastasis ◽

The lymphocyte function–associated antigen-1 (LFA-1) (also CD11a/CD18 and αLβ2), is just one of many integrins in the human body, but its significance derives from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1. A more detailed examination of LFA’s role within B-cell chronic lymphocytic leukemia is made. Finally, we discuss the role of LFA-1-harboring exosomes in tumor growth and metastasis.

Selective cytotoxic activity of cyclosporins against tumor cells from patients with B cell chronic lymphocytic leukemia

European Journal of Pharmacology Environmental Toxicology and Pharmacology ◽

10.1016/0926-6917(92)90035-b ◽

1992 ◽

Vol 228 (4) ◽

pp. 237-240

Author(s):

Rolf Larsson ◽

Bertil Jonsson ◽

Katalin Csoka ◽

Jörgen Kristensen ◽

Kenneth Nilsson ◽

...

Keyword(s):

B Cell ◽

Cytotoxic Activity ◽

Tumor Cells ◽

Lymphocytic Leukemia ◽

Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal Antibody (Rituximab, IDEC-C2B8)

Blood ◽

10.1182/blood.v94.7.2217.419k02_2217_2224 ◽

1999 ◽

Vol 94 (7) ◽

pp. 2217-2224 ◽

Cited By ~ 420

Author(s):

U. Winkler ◽

M. Jensen ◽

O. Manzke ◽

H. Schulz ◽

V. Diehl ◽

...

Keyword(s):

Adverse Events ◽

B Cell ◽

Tumor Cells ◽

Lymphocytic Leukemia ◽

Low Grade ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Anti Cd20 ◽

Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin’s lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 × 109/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 × 109/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 × 109/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 × 109/L peripheral tumor cells (P= .0017). Due to massive side effects in the first patient treated with 375 mg/m2 in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m2 dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 × 375 mg/m2 rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.

All You Need Is a Mir-acle: The Role of Nontranslated RNAs in the Suppression of B Cell Chronic Lymphocytic Leukemia

Cancer Cell ◽

10.1016/j.ccr.2009.12.029 ◽

2010 ◽

Vol 17 (1) ◽

pp. 3-4 ◽

Cited By ~ 7

Author(s):

Peter Lichter

Keyword(s):

B Cell ◽

Lymphocytic Leukemia ◽

Somatic ATM Mutations Indicate a Pathogenic Role of ATM in B-Cell Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v94.2.748 ◽

1999 ◽

Vol 94 (2) ◽

pp. 748-753 ◽

Cited By ~ 194

Author(s):

Claudia Schaffner ◽

Stephan Stilgenbauer ◽

Gudrun A. Rappold ◽

Hartmut Döhner ◽

Peter Lichter

Keyword(s):

B Cell ◽

Point Mutation ◽

Mutation Analysis ◽

Germ Line ◽

Lymphocytic Leukemia ◽

Pathogenic Role ◽

Atm Gene ◽

Abstract Deletion in chromosome bands 11q22-q23 is one of the most common chromosome aberrations in B-cell chronic lymphocytic leukemia (B-CLL). It is associated with extensive lymph node involvement and poor survival. The minimal consensus deletion comprises a segment, which contains the ATM gene presenting an interesting candidate gene, as mutations in ATM predispose A-T patients to lymphoid malignancies. To investigate a potential pathogenic role of ATM in B-cell tumorigenesis, we performed mutation analysis of ATM in 29 malignant lymphomas of B-cell origin (B-CLL = 27; mantle cell lymphoma, [MCL] = 2). Twenty-three of these carried an 11q22-q23 deletion. In five B-CLLs and one MCL with deletion of one ATMallele, a point mutation in the remaining allele was detected, which resulted in aberrant transcript splicing, alteration, or truncation of the protein. In addition, mutation analysis identified point mutations in three cases without 11q deletion: two B-CLLs with one altered allele and one MCL with both alleles mutated. In four cases analyzed, theATM alterations were not present in the germ line indicating a somatic origin of the mutations. Our study demonstrates somatic disruption of both alleles of the ATM gene by deletion or point mutation and thus its pathogenic role in sporadic B-cell lineage tumors.

Somatic ATM Mutations Indicate a Pathogenic Role of ATM in B-Cell Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v94.2.748.414k02_748_753 ◽

1999 ◽

Vol 94 (2) ◽

pp. 748-753 ◽

Cited By ~ 3

Author(s):

Claudia Schaffner ◽

Stephan Stilgenbauer ◽

Gudrun A. Rappold ◽

Hartmut Döhner ◽

Peter Lichter

Keyword(s):

B Cell ◽

Point Mutation ◽

Mutation Analysis ◽

Germ Line ◽

Lymphocytic Leukemia ◽

Pathogenic Role ◽

Atm Gene ◽

Deletion in chromosome bands 11q22-q23 is one of the most common chromosome aberrations in B-cell chronic lymphocytic leukemia (B-CLL). It is associated with extensive lymph node involvement and poor survival. The minimal consensus deletion comprises a segment, which contains the ATM gene presenting an interesting candidate gene, as mutations in ATM predispose A-T patients to lymphoid malignancies. To investigate a potential pathogenic role of ATM in B-cell tumorigenesis, we performed mutation analysis of ATM in 29 malignant lymphomas of B-cell origin (B-CLL = 27; mantle cell lymphoma, [MCL] = 2). Twenty-three of these carried an 11q22-q23 deletion. In five B-CLLs and one MCL with deletion of one ATMallele, a point mutation in the remaining allele was detected, which resulted in aberrant transcript splicing, alteration, or truncation of the protein. In addition, mutation analysis identified point mutations in three cases without 11q deletion: two B-CLLs with one altered allele and one MCL with both alleles mutated. In four cases analyzed, theATM alterations were not present in the germ line indicating a somatic origin of the mutations. Our study demonstrates somatic disruption of both alleles of the ATM gene by deletion or point mutation and thus its pathogenic role in sporadic B-cell lineage tumors.