Anti-SEMA4D and anti–CTLA-4 treatment is synergistic and increases the frequency of tumor-specific TILs and secretion of proinflammatory cytokines, while.

Slides:

Advertisements

Similar presentations

AF647-RIS is internalized by TAMs in vivo.

Advertisements

Anti–4-1BB/PD-1 combination enriched CD8+ T cells in TILs

Uptake of T-MPs for DC maturation and antigen presentation.

Sunitinib plus rMVA–CEA–TRICOM vaccine decreased tumor burden and increased intratumoral infiltration of T lymphocytes in the MC38-CEA colon carcinoma.

Triggering PD-1 in B cells suppresses tumor-specific immunity and promotes disease progression. Triggering PD-1 in B cells suppresses tumor-specific immunity.

IHC staining of FFPE esophageal tissues in tissue microarrays (×20).

Frequencies of immune cell types show much stronger variations between tumor types in the tumor infiltrate compared with the spleen and tumor-draining.

H31m1-PDL1 cells form progressively growing tumors in WT mice.

IL-6 is dispensable for the suppressive activity of MDSC on primary CD4+ T-cell activation. IL-6 is dispensable for the suppressive activity of MDSC on.

Cetuximab treatment increases IFNγ receptor 1 expression.

Functions of myeloid cells.

Anti–4-1BB/PD-1 combination enhanced antigen-specific T-cell response.

Volume 28, Issue 4, Pages (April 2008)

Gr-1+ MDSC in tumor-bearing mice produce IL-6.

Volume 28, Issue 4, Pages (October 2015)

B7-H4 expression correlates with MHC-I expression and improved prognosis in patients with breast cancer. B7-H4 expression correlates with MHC-I expression.

Vascular HR ligand expression depends on tumor anatomical location.

2aG4 directly induces monocytic MDSCs to differentiate into dendritic cells and macrophages by binding to phosphatidylserine on their cell surface. 2aG4.

Arp2/3-mediated formation of nuclear actin networks is essential for CD4+ T cell effector functions. Arp2/3-mediated formation of nuclear actin networks.

CD8+ T cells were immunomodulated and required for the efficacy of anti–4-1BB/anti–PD-1 combination treatment. CD8+ T cells were immunomodulated and required.

Highly related T9 and T3 sarcoma cells show distinct tumor growth patterns but similar PD-L1 expression kinetics in vivo. Highly related T9 and T3 sarcoma.

CHL cell lines induce a suppressive Treg phenotype in cocultured CD4+ T cells. cHL cell lines induce a suppressive Treg phenotype in cocultured CD4+ T.

CPI-444 efficacy requires CD8+ T cells and is associated with increased CD73 expression. CPI-444 efficacy requires CD8+ T cells and is associated with.

Adaptive NK cells resist immunosuppression in the tumor microenvironment. Adaptive NK cells resist immunosuppression in the tumor microenvironment. FACS-sorted.

Reduced tumor growth in CCR5-deficient mice is associated with perturbed killing ability of Treg cells. Reduced tumor growth in CCR5-deficient mice is.

coTCRcys-transduced T cells control tumor growth in vivo.

Antigen-specific CD8+ T cells express higher levels of PD-1 in animals that received the optimized SSX2 vaccine. Antigen-specific CD8+ T cells express.

Quercetin induces arrest in G1 phase of cell cycle in P39 xenografts.

PD-1 inhibition stimulates the proliferation and cytokine secretion of exhausted/senescent CD8+ T cells in vitro. PD-1 inhibition stimulates the proliferation.

Vascular staining in CWR22R xenograft tumors.

A, iDC (top) or mDC (bottom) were loaded with or without 10 pfu/cell reovirus, and cultured with Mel-888 cells in the presence of blocking serum. A, iDC.

PD-L1 expressed on edited T3 sarcoma cells prevents their immune elimination. PD-L1 expressed on edited T3 sarcoma cells prevents their immune elimination.

Induction of cytotoxic activity in humanized SCC3 tumor-bearing mice treated with anti-PD-1 antibody. Induction of cytotoxic activity in humanized SCC3.

PVHA increased anti-PD-L1–mediated growth inhibition in 4T1/HAS3 tumors. PVHA increased anti-PD-L1–mediated growth inhibition in 4T1/HAS3 tumors. A, 4T1/HAS3.

ADU-S100–mediated tumor clearance is dependent on CD4+, CD8+ T cells, and NK cells. ADU-S100–mediated tumor clearance is dependent on CD4+, CD8+ T cells,

5FU-induced specific activation of CD8+ T cells.

CD4+ and CD8+ TILs express surface CD137.

CDN–treated MOC1 tumors demonstrate enhanced activation of innate and antigen-specific adaptive immunity. CDN–treated MOC1 tumors demonstrate enhanced.

Dual blockade of PD-1 and CTLA-4 directly activates CD4+Foxp3− cells in the absence of CD8+ or CD4+Foxp3+ cells. Dual blockade of PD-1 and CTLA-4 directly.

Irradiated whole-cell vaccination with MOC1, but not MOC2, induces immunologic memory. Irradiated whole-cell vaccination with MOC1, but not MOC2, induces.

Canonical but not adaptive NK-cell function is suppressed by Tregs.

Dysregulated NF-κB activation in Il1r8+/+/lpr and Il1r8−/−/lpr mice.

Combination CDN and PD-L1 mAb treatment of established MOC1 tumors produces consistent tumor rejection. Combination CDN and PD-L1 mAb treatment of established.

DAC treatment alters immune cell composition and enhances cytokine production in the peritoneal lavage. DAC treatment alters immune cell composition and.

Deletion of Tgfbr2 in myeloid cells elevated IFN-γ production in CD8+ T cells, and systemic IFN-γ neutralization diminished metastasis inhibition in Tgfbr2MyeKO.

Immunophenotypic analysis of TILs in B16 and K1735 melanoma following combination therapy with antibodies targeting PS and PD-1. Immunophenotypic analysis.

PD-1 and CD103 are coexpressed on CD8+ T cells but demonstrate distinct mechanisms of regulation. PD-1 and CD103 are coexpressed on CD8+ T cells but demonstrate.

Anti-SEMA4D antibody regulates immune-cell infiltration and inhibits growth of Tubo.A5 orthotopic mammary carcinoma. Anti-SEMA4D antibody regulates immune-cell.

Effect of inhibiting HO-1 on adaptive immune- and cytokine-dependent regulation of tumor growth. Effect of inhibiting HO-1 on adaptive immune- and cytokine-dependent.

CPI-444 enhances T-cell activation in MC38 tumors.

Anti-CD40 activates TAMs and recruits inflammatory monocytes.

The CCR5+ population of SUM-159 cells is enriched with tumor-initiating cells. The CCR5+ population of SUM-159 cells is enriched with tumor-initiating.

Increased expression of angiogenic factors and inflammatory cytokines in mice exposed to hypoxia. Increased expression of angiogenic factors and inflammatory.

Immune checkpoint molecule expression in primary and secondary tumors following radiotherapy. Immune checkpoint molecule expression in primary and secondary.

Serum IFNγ and immune responses following tecemotide/cisplatin combination treatment in a urethane-induced hMUC1.Tg lung cancer mouse model. Serum IFNγ.

The effect of TGFβ on the post-RT increase of Tregs in tumors.

Anti–TGF-β1 antibody neutralizes APB-mediated immune suppression.

LSECtin, expressed by B16 cells, inhibits the tumor-specific immune responses both in vivo and in vitro. LSECtin, expressed by B16 cells, inhibits the.

Loss of polarity gene Dlg1 leads to an expansion of C'-1 stage cells during pre-B cell differentiation. Loss of polarity gene Dlg1 leads to an expansion.

Mutation of the Smad3 linker phosphorylation sites in 4T1 cells reduces putative stem cell population and tumor initiating frequency of cells from the.

Increased tumorigenic activities of TIM-3–expressing RCC cells.

The effect of βAR signaling on the generation of a cytotoxic CD8+ T-cell response in vivo. The effect of βAR signaling on the generation of a cytotoxic.

Effect of HDC on the ROS production in mouse lungs after melanoma cell inoculation. Effect of HDC on the ROS production in mouse lungs after melanoma cell.

IL2Cx alone or in combination with anti–CTLA-4 increases the CD8/Treg ratio in the tumor. IL2Cx alone or in combination with anti–CTLA-4 increases the.

Recruitment of CD8+, CD4+, and Foxp3+ cells into oral lesions in response to anti–PD-1 treatment. Recruitment of CD8+, CD4+, and Foxp3+ cells into oral.

EC-derived SP cells are targeted by CD30.CAR T cells.

Bezafibrate increases the number of effector CTLs by enhancing their survival capacity and proliferation. Bezafibrate increases the number of effector.

Coincidence and prognostic significance of PD-1+ and CD103+ cells in HGSC. Serial sections from the 490-case TMA were stained with antibodies to CD103.

Phenotyping of T cells. Phenotyping of T cells. Circulating lymphocytes from a tumor-naïve C57BL/6 mice (left column) were compared with those from C57BL/6.

IHC staining of FFPE esophageal tissues in tissue microarrays (×20).

Presentation transcript:

Anti-SEMA4D and anti–CTLA-4 treatment is synergistic and increases the frequency of tumor-specific TILs and secretion of proinflammatory cytokines, while reducing suppressive signals. Anti-SEMA4D and anti–CTLA-4 treatment is synergistic and increases the frequency of tumor-specific TILs and secretion of proinflammatory cytokines, while reducing suppressive signals. Tumors and spleens were isolated from Colon26 tumor–bearing mice following treatment. CD45+ TILs were enriched from dissociated tumor using CD45 Automacs selection. Because of the small tumor volumes, it was necessary to pool samples from each treatment group for FACS and functional assays. For functional assays, TILs were pooled from 9 to 18 mice, to make up a total tumor volume of at least 1.5 g/group, and spleens were pooled from 4 to 5 mice/group; assay replicates are shown. For FACS analysis, three to four pools (3–6 tumors/pool) were assessed for each treatment group; biologic replicates are shown. Individual tumors (n = 6–10/group) were independently assessed by IHC and quantified using entire FFPE tumor sections, which were stained and quantitated. A, percent CD8+ cells were assessed by FACS. B, IFNγ-secreting functional CD8+ cells were measured by ELISPOT. C, Teff:Treg ratios were determined by FACS (left), and IHC (right); the ratio of Teff cells/Treg cells was determined for each pool or animal. D, tumor sections were also stained by IHC for monocyte-activation marker CD86. E, CD45+ TILs were cultured ex vivo for 48 hours and assayed for cytokine secretion using CBA analysis. Elizabeth E. Evans et al. Cancer Immunol Res 2015;3:689-701 ©2015 by American Association for Cancer Research