Differential Requirement for CD70 and CD80/CD86 in Dendritic Cell-Mediated Activation of Tumor-Tolerized CD8 T Cells

Bak, S. Peter; Barnkob, Mike Bogetofte; Bai, Ailin; Higham, Eileen M.; Wittrup, K. Dane; Chen, Jianzhu

doi:10.4049/jimmunol.1201271

Cited by 36 publications

(32 citation statements)

References 35 publications

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“…These results suggest that CD4 T cells play a more dominant role in the PLX4720-mediated anti-tumor response than CD8 T cells. Note, we also examined whether the elevated CD70 expression on APCs after PLX4720 therapy contributed to its ability to reverse tolerant CTLs and retard tumor growth (14, 15, 34), but found that blocking CD70 did not perturb the ability of PLX4720 to inhibit tumor progression in any detectable manner (Supplementary Figure 6). …”

Section: Resultsmentioning

confidence: 99%

Immune-Based Antitumor Effects of BRAF Inhibitors Rely on Signaling by CD40L and IFNγ

et al. 2014

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B-RafV600E inhibitors have been suggested to promote tumor regression with the help of host immunity, but this hypothesis has not been examined directly in detail. In this study, we profiled immunological changes in the tumor microenvironment and tumor infiltrating lymphocytes (TILs) in a B-RafV600E/Pten-driven murine model of melanoma, after administration of the BRafV600E small molecule inhibitor PLX4720. In this model, we found that as tumors developed they gradually acquired immunosuppressive features, including accumulation of regulatory T cells (Tregs) and CD11b+/Gr-1+ myeloid cells and loss of Th1 effector functions on CD4+ TILs, such as CD40L and IFN-γ expression. PLX4720 administration promoted development of a more immune stimulatory microenvironment associated with a relative increase in CD40L and IFNγ expression on intratumoral CD4+ TILs and a reduced accumulation of Tregs and CD11b+/Gr-1+ myeloid cells. Strikingly, CD40L or IFNγ blockade compromised the ability of PLX4720 to inhibit melanoma growth. Supporting this result, agonistic CD40 antibody was sufficient to evoke anti-tumor immunity and suppress tumor growth in tumor-bearing mice. Taken together, our results establish the critical role of immune-related changes with key contributions for CD40L and IFNγ signaling in the anti-tumor responses triggered in vivo by BRafV600E inhibitors.

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Section: Resultsmentioning

confidence: 99%

Immune-Based Antitumor Effects of BRAF Inhibitors Rely on Signaling by CD40L and IFNγ

et al. 2014

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“…Nevertheless, expression of CD70 on tumor cells or antigenpresenting cells has also been described to have anti-tumoral effects (Arens et al, 2004;Bak et al, 2012;Couderc et al, 1998;Glouchkova et al, 2009;Kelly et al, 2002;Lorenz et al, 1999). This raises the question if CD70 blocking antibodies might also have the opposite effect on anti-tumoral immunity by blocking the stimulatory function of CD70 on antigen-presenting cells and NK cells or by depleting activated T cells, as suggested by the CD27-agonistic antibody, CDX-1127 (Thomas et al, 2014).…”

Section: Discussion: Are We Targeting the Right Molecule?mentioning

confidence: 98%

CD70: An emerging target in cancer immunotherapy

Jacobs

Deschoolmeester

Zwaenepoel

et al. 2015

Pharmacology & Therapeutics

155

150

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Over the last decades, advances in the knowledge of immunology have led to the identification of immune checkpoints, reinvigorating cancer immunotherapy. Although normally restricted to activated T and B cells, constitutive expression of CD70 in tumor cells has been described. Moreover, CD70 is implicated in tumor cell and regulatory T cell survival through interaction with its ligand, CD27. In this review, we summarize the targetable expression patterns of CD70 in a wide range of malignancies and the promising mechanism of anti-CD70 therapy in stimulating the anti-tumor immune response. In addition, we will discuss clinical data and future combination strategies.

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“…S7B). Many of these genes have been shown to be critical for antitu-mor responses, including those involved in CD8 + T cell activation and costimulation [ H2-m2 (MHC-I), Cd40 , Cd70 , and Icam1 ] (20–22); DC maturation ( Relb and Ifngr2 ) (23, 24); antigen processing and cross presentation ( Tapbp , Rab27a , and Slc11a1 ) (25–27); chemokine-mediated recruitment of immune cells to the tumor microenvironment ( Cxcl9 , Cx3cl1 , and Cxcr4 ) (28–30); and type I interferon signaling ( Irf1 , Ifnar2 , Oas2 , Ifi35 , and Ifitm1 ) (31, 32) (Fig. 4D and fig.…”

mentioning

confidence: 99%

Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy

Sivan

Corrales

Hubert

et al. 2015

Science

3,096

2,634

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T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)–specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8+ T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

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Differential Requirement for CD70 and CD80/CD86 in Dendritic Cell-Mediated Activation of Tumor-Tolerized CD8 T Cells

Cited by 36 publications

References 35 publications

Immune-Based Antitumor Effects of BRAF Inhibitors Rely on Signaling by CD40L and IFNγ

Immune-Based Antitumor Effects of BRAF Inhibitors Rely on Signaling by CD40L and IFNγ

CD70: An emerging target in cancer immunotherapy

Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy

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