Induction of CD11a/leukocyte function antigen-1 and CD54/intercellular adhesion molecule-1 on hairy cell leukemia cells is accompanied by enhanced susceptibility to T-cell but not lymphokine-activated killer- cell cytotoxicity [see comments]

Jh, Jansen; Harst, D van der; Wientjens, G. J. H. M.; Kooy-Winkelaar, YM; Brand, Anneke; Willemze, Rein; Kluin-Nelemans, Hanneke C.

doi:10.1182/blood.v80.2.478.bloodjournal802478

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD54 (ICAM‐1) mediates a series of immune mechanisms including non‐MHC‐restricted interaction with killer cells and delivery of a costimulatory activation signal to MHC class I‐restricted CD8+ T cells via interaction with LFA‐1 (Jansen et al, 1992; Vanky et al, 1990; Ybarrondo et al, 1994). Earlier studies from our laboratory demonstrated a deficiency in CD54 (ICAM‐1) expression on breast cancer cells, which led us to speculate that this defect could contribute to their escape from lytic effector cell function exerted by lymphokine‐activated killer cells (Budinsky et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer

et al. 2000

View full text Add to dashboard Cite

Previous experiments from our laboratory have shown that immune mechanisms aiming at the destruction of tumour cells including the recognition of target cells and their elimination via the expression of intercellular adhesion molecule‐1 (ICAM‐1; CD54), the production of tumour necrosis factor‐α (TNF‐α) by monocytes and appropriate function of lymphocyte subpopulations were defective in breast cancer. Previous observations were extended to assess expression levels and regulatory mechanisms of costimulatory molecules CD54, CD80 and CD86 on monocytes derived from patients with early breast cancer (EBC). In addition, antigen presentation by antigen‐presenting cells (APC) was analyzed within this context. We report that monocytes derived from patients with EBC exhibited significantly decreased expression levels of CD54 (p = 0.0002), CD80 (p = 0.009) and CD 86 (p = 0.002) compared with monocytes derived from healthy females. Simultaneously, lipopolysaccharide (LPS)‐induced TNF‐α production of monocytes was found to be defective in patients with EBC. Finally, T‐cell proliferation in response to tetanus toxoid (TT) was significantly decreased in patients with EBC compared with healthy control females (p < 0.0001). Furthermore, T‐cell proliferation in response to TT‐pulsed APC derived from healthy controls was significantly inhibited in the presence of anti‐CD54 and/or anti‐CD80 antibodies in a dose‐dependent manner, thus corroborating the necessity of the presence of CD54 and CD80 as costimulatory molecules in the present setting. We conclude that monocytes derived from patients with EBC showed a simultaneous defect of expression of CD54 and its regulation via TNF‐α, CD80 and CD86 as well as T‐cell proliferation following exposure to TT‐pulsed APC. Based upon these findings, it is speculated that defects in costimulatory molecule expression might contribute to tolerance of the immune system towards the presence of malignant cells in patients with EBC. Int. J. Cancer 88:239–244, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer

et al. 2000

View full text Add to dashboard Cite

show abstract

“…This finding is consistent with previous literature showing that LFA-1 and ICAM-1 play important roles in the adhesion, migration, and invasion of lymphoma cells. [37][38][39][40][41][42] Expression and BLNK association of RAC2 are downregulated by ibrutinib in sensitive cells but not in resistant cells…”

Section: Bcr Signaling and Cell Adhesion Transcriptional Programs Are Inhibited In A Coordinated Fashion By Ibrutinib In Drug-sensitive Bmentioning

confidence: 99%

Inhibition of B-cell receptor signaling disrupts cell adhesion in mantle cell lymphoma via RAC2

Wang

Franzen

et al. 2021

Blood Advances

View full text Add to dashboard Cite

Inhibition of the B-cell receptor (BCR) signaling pathway is highly effective in B-cell neoplasia through Bruton tyrosine kinase inhibition by ibrutinib. Ibrutinib also disrupts cell adhesion between a tumor and its microenvironment. However, it is largely unknown how BCR signaling is linked to cell adhesion. We observed that intrinsic sensitivities of mantle cell lymphoma (MCL) cell lines to ibrutinib correlated well with their cell adhesion phenotype. RNA-sequencing revealed that BCR and cell adhesion signatures were simultaneously downregulated by ibrutinib in the ibrutinib-sensitive, but not ibrutinib-resistant, cells. Among the differentially expressed genes, RAC2, part of the BCR signature and a known regulator of cell adhesion, was downregulated at both the RNA and protein levels by ibrutinib only in sensitive cells. RAC2 physically associated with B-cell linker protein (BLNK), a BCR adaptor molecule, uniquely in sensitive cells. RAC2 reduction using RNA interference and CRISPR impaired cell adhesion, whereas RAC2 overexpression reversed ibrutinib-induced cell adhesion impairment. In a xenograft mouse model, mice treated with ibrutinib exhibited slower tumor growth, with reduced RAC2 expression in tissue. Finally, RAC2 was expressed in ∼65% of human primary MCL tumors, and RAC2 suppression by ibrutinib resulted in cell adhesion impairment. These findings, made with cell lines, a xenograft model, and human primary lymphoma tumors, uncover a novel link between BCR signaling and cell adhesion. This study highlights the importance of RAC2 and cell adhesion in MCL pathogenesis and drug development.

show abstract

“…42 Indeed, CD54, CD11a and CD58 are known to facilitate contact between target cells and cytotoxic effectors. 23,[42][43][44] However, these CAMs were highly expressed in the other high grade NHL of our series. In this context, their role may be to offer a growth advantage by preferential interaction between the malignant B cells themselves (via their simultaneous expression of the CD54/LFA-1 ligand pair), as well as with environmental cells.…”

Section: Discussionmentioning

confidence: 92%

True

1999

Leukemia

View full text Add to dashboard Cite

The expression of five cellular adhesion molecules (CAMs), CD54, CD58, CD11a, CD29 and CD49d, was studied in 113 B cell non-Hodgkin's lymphomas (NHL) and in normal B cells from 12 control lymph nodes. Rather than reporting the percentage of positive cells, which does not discriminate between NHL subtypes, we quantified the intensity of CAM expression using flow cytometry. Apart from CD49d the expression of all these CAMs was statistically different among the NHL subtypes as defined by the REAL classification. Low grade NHL-small lymphocytic, follicular and mantle cell lymphoma--which are derived from quiescent cells and show an indolent disease course, expressed low levels of CAMs. Conversely, high grade NHL-diffuse large cell lymphoma--which are derived from proliferating cells and are clinically aggressive, expressed high levels of CAMs. These results indicate that in malignant NHL B cell tumour growth and clinical aggressiveness may be related to the adhesive capacities of the tumour cells.

show abstract

Induction of CD11a/leukocyte function antigen-1 and CD54/intercellular adhesion molecule-1 on hairy cell leukemia cells is accompanied by enhanced susceptibility to T-cell but not lymphokine-activated killer- cell cytotoxicity [see comments]

Cited by 3 publications

References 0 publications

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer

Inhibition of B-cell receptor signaling disrupts cell adhesion in mantle cell lymphoma via RAC2

True

Contact Info

Product

Resources

About