EMAIL THIS PAGE TO A FRIEND

Proceedings of the National Academy of Sciences of the United States of America

Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients.


PMID 25918390

Abstract

Enhancing immune responses with immune-modulatory monoclonal antibodies directed to inhibitory immune receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) or PD-1/PD-L1. Treatment with ipilimumab, a fully human CTLA-4-specific mAb, showed durable clinical efficacy in metastatic melanoma; its mechanism of action is, however, only partially understood. This is a study of 29 patients with advanced cutaneous melanoma treated with ipilimumab. We analyzed peripheral blood mononuclear cells (PBMCs) and matched melanoma metastases from 15 patients responding and 14 not responding to ipilimumab by multicolor flow cytometry, antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and immunohistochemistry. PBMCs and matched tumor biopsies were collected 24 h before (i.e., baseline) and up to 4 wk after ipilimumab. Our findings show, to our knowledge for the first time, that ipilimumab can engage ex vivo FcγRIIIA (CD16)-expressing, nonclassical monocytes resulting in ADCC-mediated lysis of regulatory T cells (Tregs). In contrast, classical CD14(++)CD16(-) monocytes are unable to do so. Moreover, we show that patients responding to ipilimumab display significantly higher baseline peripheral frequencies of nonclassical monocytes compared with nonresponder patients. In the tumor microenvironment, responders have higher CD68(+)/CD163(+) macrophage ratios at baseline and show decreased Treg infiltration after treatment. Together, our results suggest that anti-CTLA-4 therapy may target Tregs in vivo. Larger translational studies are, however, warranted to substantiate this mechanism of action of ipilimumab in patients.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

GW22783 Anti-CD14 antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB2500215
Anti-CD14 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1405579
Anti-CD14 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA001887
Anti-CD14 antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA002127
Anti-CD14 antibody produced in rabbit, Ab3, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1301555
ANTI-CD163 (N-TERM) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB1401062
Anti-CD68 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2700244
Anti-CD68 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA048982
Anti-CD68 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2107746
Anti-CD68 antibody produced in rabbit, affinity isolated antibody, lyophilized powder
SAB2107747
Anti-CD68 antibody produced in rabbit, affinity isolated antibody
SAB2700362
Anti-Foxp3 (C-terminal) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB1407427
Anti-FOXP3 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB1410887
Anti-FOXP3 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
AMAB90897
Monoclonal Anti-CD14 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1637, purified immunoglobulin, buffered aqueous glycerol solution
AMAB90898
Monoclonal Anti-CD14 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1638, purified immunoglobulin, buffered aqueous glycerol solution
C7673
Monoclonal Anti-CD14 antibody produced in mouse, clone UCHM-1, purified immunoglobulin, buffered aqueous solution
SAB4700097
Monoclonal Anti-CD14 antibody produced in mouse, clone MEM-15, purified immunoglobulin, buffered aqueous solution
SAB4700103 Monoclonal Anti-CD14 antibody produced in mouse, clone MEM-18, purified immunoglobulin, buffered aqueous solution
SAB4700669 Monoclonal Anti-CD14 antibody produced in mouse, clone B-A8, purified immunoglobulin, buffered aqueous solution
SAB4700268 Monoclonal Anti-CD16 antibody produced in mouse, clone MEM-168, purified immunoglobulin, buffered aqueous solution
SAB4700269 Monoclonal Anti-CD16 antibody produced in mouse, clone LNK16, purified immunoglobulin, buffered aqueous solution
SAB4700274 Monoclonal Anti-CD16 antibody produced in mouse, clone 3G8, purified immunoglobulin, buffered aqueous solution
SAB4700276 Monoclonal Anti-CD16 antibody produced in mouse, clone MEM-154, purified immunoglobulin, buffered aqueous solution
AMAB90873
Monoclonal Anti-CD68 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1338, purified immunoglobulin, buffered aqueous glycerol solution
AMAB90874
Monoclonal Anti-CD68 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1346, purified immunoglobulin, buffered aqueous glycerol solution
SAB4700610 Monoclonal Anti-FOXP3 antibody produced in mouse, clone 3G3, purified immunoglobulin, buffered aqueous solution
SAB5300461
Monoclonal Anti-FOXP3 antibody produced in mouse, clone 2A11G9, ascites fluid
SAB5300462
Monoclonal Anti-FOXP3 antibody produced in mouse, clone 4C7, ascites fluid