2014
DOI: 10.1084/jem.20130590
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Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy

Abstract: CTLA-4 blockade leads to enhanced activation of tumor-reactive T cells with concomitant up-regulation of ICOS, thus enabling their responses to be enhanced by ICOS engagement.

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Cited by 256 publications
(200 citation statements)
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References 26 publications
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“…Administration of peptide vaccine alone increased the frequency of ICOS + CD8 T cells greater than fourfold relative to untreated mice. In accordance with recent publications, αCTLA-4 therapy also increased the infiltration of tumors by ICOS + T cells, although not to a level that reached statistical significance (22,23). Addition of the peptide vaccine to αCTLA-4 promoted a threefold higher frequency of ICOS + CD8 T-cell infiltration (28% versus 9%) relative to antibody monotherapy.…”
Section: Intranasal Vaccination With Hpv E6/e7 Peptides In Combinatiosupporting
confidence: 89%
See 1 more Smart Citation
“…Administration of peptide vaccine alone increased the frequency of ICOS + CD8 T cells greater than fourfold relative to untreated mice. In accordance with recent publications, αCTLA-4 therapy also increased the infiltration of tumors by ICOS + T cells, although not to a level that reached statistical significance (22,23). Addition of the peptide vaccine to αCTLA-4 promoted a threefold higher frequency of ICOS + CD8 T-cell infiltration (28% versus 9%) relative to antibody monotherapy.…”
Section: Intranasal Vaccination With Hpv E6/e7 Peptides In Combinatiosupporting
confidence: 89%
“…Whereas CTLA-4 and PD-1 blockade are known to promote ICOS up-regulation, 4-1BB agonist does not (7). Given that ICOS expression has been associated with enhanced T-cell effector function and prolonged survival, we hypothesize that the ICOS + ThEO and TcEO T cells formed by the combination of vaccination and α4-1BB may have an unparalleled potential to eliminate established tumors (22,23). Our data suggest that either direct or indirect action of the αGalCer adjuvant at the vaccine site must contribute to ICOS induction as peptides alone or α4-1BB antibody alone have not been reported to have this effect.…”
Section: Discussionmentioning
confidence: 94%
“…Furthermore, the treatment with Ipilimumab resulted in higher CD4+ ICOS+ T frequency and IFN-y levels in malignant prostate tissue [31]. Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy [32].…”
Section: Immune Checkpointsmentioning
confidence: 99%
“…Furthermore, the treatment with Ipilimumab resulted in higher CD4+ ICOS+ T frequency and IFN-y levels in malignant prostate tissue [31]. Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy [32].The treatment with anti-CTLA-4 enhances the production of IFN-γ, which is a critical cytokine for tumor immune responses. The loss of the IFN-γ signaling pathway is highly associated with primary resistance to Ipilimumab.…”
mentioning
confidence: 99%
“…16,17), and Tim3 (18,19) and for agonists that activate immune stimulatory pathways, such as 4-1BB (CD-137; refs. 20, 21), OX40 (22,23), inducible T-cell costimulator (24), and GITR. Indeed, in preclinical melanoma studies, the combination of multiple immunotherapies (e.g., anti-PD-1 and anti-CTLA-4) has shown significantly better efficacy than single-agent therapy.…”
Section: Introductionmentioning
confidence: 99%