Contribution of Fcγ receptor IIB to creating a suppressive tumor microenvironment in a mouse model

Kasahara, Yuki; Shirota, Hidekazu; Umegaki, Sho; Ishioka, Chikashi

doi:10.1007/s00262-019-02413-w

Cited by 7 publications

(8 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, targeted disruption of inhibitory FcRs is a relatively new and promising approach to enhance ADCP therapeutically. [49][50][51] Nevertheless, additional investigations are required to definitively establish the role of FcgRIIb in hypophagia.…”

Section: Discussionmentioning

confidence: 99%

Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance

Pinney

Rivera-Escalera

Chu

et al. 2020

Blood

View full text Add to dashboard Cite

Macrophage antibody dependent cellular phagocytosis (ADCP) is a major cytotoxic mechanism for both therapeutic unconjugated monoclonal antibodies (mAb) such as rituximab, and antibody induced hemolytic anemia and immune thrombocytopenia. Here, we studied the mechanisms controlling the rate and capacity of macrophages to carry out ADCP in settings of high target to effector cell ratio such as that seen in patients with circulating tumor burden in leukemic phase disease. Using quantitative live-cell imaging of primary human and mouse macrophages we found that, upon initial challenge with mAb-opsonized lymphocytes, macrophages undergo a brief burst (<1hr) of rapid phagocytosis which is then invariably followed by a sharp reduction in phagocytic activity that can persist for days. This previously unknown refractory period of ADCP, or "hypophagia," was observed in all macrophage/mAb/target cell conditions tested in vitro, and was also seen in vivo in Kupffer cells from mice induced to undergo successive rounds of ⍺CD20 mAb-dependent clearance of circulating B cells. Importantly, hypophagia had no effect on antibody-independent phagocytosis and did not alter macrophage viability. In mechanistic studies we found that the rapid loss of activating Fc receptors from the surface and their subsequent proteolytic degradation is the primary mechanism responsible for the loss of ADCP activity in hypophagia. These data suggest hypophagia is a critical limiting step in macrophage-mediated clearance of cells via ADCP and that understanding such limitations to innate immune system cytotoxic capacity will aid in the development of mAb regimens that could optimize ADCP and improve patient outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance

Pinney

Rivera-Escalera

Chu

et al. 2020

Blood

View full text Add to dashboard Cite

show abstract

“…Alterations in the APP are known to be associated with immune evasion and can result in impaired antitumor responses and therapy resistance 45 . Additionally, the blockade of the interaction between the inhibitory Fc receptor FcγRIIB and immune complexes in mouse models has been proposed as an approach for cancer immunotherapy 46 . Thus, we identified immune cell players and components of specific pathways that can be further targeted to enhance the immunogenicity in HNSCC or that can be explored as markers of immunotherapy resistance.…”

Section: Discussionmentioning

confidence: 99%

Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer

et al. 2022

View full text Add to dashboard Cite

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

show abstract

“…Alterations in the APP are known to be associated with immune evasion and can result in impaired antitumor responses and therapy resistance (Gettinger et al, 2017;Sade-Feldman et al, 2017). Additionally, blockade of the interaction between the inhibitory Fc receptor FcγRIIB and immune complexes in mouse models has been proposed as an approach for cancer immunotherapy (Kasahara et al, 2019). Thus, we identified immune cell players and components of specific pathways that can be further targeted to enhance the immunogenicity in HNSCC or that can be further explored as markers of immunotherapy resistance.…”

Section: Discussionmentioning

confidence: 99%

Wiring multiple microenvironment proteomes uncovers the biology in head and neck cancer

Busso-Lopes

Rivera

Neves

et al. 2021

Preprint

View full text Add to dashboard Cite

The poor prognosis of head and neck cancer (HNC) is associated with the presence of metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identified a nodal metastasis signature in the blood and saliva. In summary, we present the deepest proteome characterization wiring multiple sampling sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

show abstract

Contribution of Fcγ receptor IIB to creating a suppressive tumor microenvironment in a mouse model

Cited by 7 publications

References 37 publications

Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance

Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance

Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer

Wiring multiple microenvironment proteomes uncovers the biology in head and neck cancer

Contact Info

Product

Resources

About