Targeting the T-Cell Co-stimulatory CD27/CD70 Pathway in Cancer Immunotherapy: Rationale and Potential

Ven, Koen van de; Borst, Jannie

doi:10.2217/imt.15.32

Cited by 130 publications

(97 citation statements)

References 84 publications

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“…Currently, a phase I study, in which the toxicity of anti-CD137 and anti-PD-1 is determined in patients with solid tumors, is in progress (NCT02179918). Combination approaches with anti-CD27 (Tnfrsf7) are also promising (125). The combination of anti-CD27 with anti-PD-1, but not anti-CTLA-4, eradicated tumors in a cervical cancer model (TC-1) (119).…”

Section: Combinations With Stimulation Of T Cell Activation (Step 3)mentioning

confidence: 99%

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

2016

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In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

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Section: Combinations With Stimulation Of T Cell Activation (Step 3)mentioning

confidence: 99%

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

2016

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“…These data indicate that a synergistic relationship exists between CD27 stimulation and CD4 + T cell help. CD27 signaling has been previously shown to drive T H 1 polarization in mouse 33 and human 34 CD4 + T cells by upregulating IL-12Rβ2 and T-bet expression and was also found to enhance their helper activity towards CD8 + T cells. 35 Additionally, we surmise that CD4 + T cell help may render CD8 + T cells more sensitive to CD27 signaling, thus amplifying the effect of αhCD27 on the CD8 + T cell response compared to the effect that αhCD27 would have in the absence of CD4 + T cell help.…”

Section: Discussionmentioning

confidence: 94%

CD27 stimulation unveils the efficacy of linked class I/II peptide vaccines in poorly immunogenic tumors by orchestrating a coordinated CD4/CD8 T cell response

Riccione

Fecci

et al. 2018

OncoImmunology

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Despite their promise, tumor-specific peptide vaccines have limited efficacy. CD27 is a costimulatory molecule expressed on CD4+ and CD8+ T cells that is important in immune activation. Here we determine if a novel CD27 agonist antibody (αhCD27) can enhance the antitumor T cell response and efficacy of peptide vaccines. We evaluated the effects of αhCD27 on the immunogenicity and antitumor efficacy of whole protein, class I-restricted, and class II-restricted peptide vaccines using a transgenic mouse expressing human CD27. We found that αhCD27 preferentially enhances the CD8+ T cell response in the setting of vaccines comprised of linked class I and II ovalbumin epitopes (SIINFEKL and TEWTSSNVMEERKIKV, respectively) compared to a peptide vaccine comprised solely of SIINFEKL, resulting in the antitumor efficacy of adjuvant αhCD27 against intracranial B16.OVA tumors when combined with vaccines containing linked class I/II ovalbumin epitopes. Indeed, we demonstrate that this efficacy is both CD8- and CD4-dependent and αhCD27 activity on ovalbumin-specific CD4+ T cells is necessary for its adjuvant effect. Importantly for clinical translation, a linked universal CD4+ helper epitope (tetanus P30) was sufficient to instill the efficacy of SIINFEKL peptide combined with αhCD27, eliminating the need for a tumor-specific class II-restricted peptide. This approach unveiled the efficacy of a class I-restricted peptide vaccine derived from the tumor-associated Trp2 antigen in mice bearing intracranial B16 tumors. CD27 agonist antibodies combined with peptide vaccines containing linked tumor-specific CD8+ epitopes and tumor-specific or universal CD4+ epitopes enhance the efficacy of active cancer immunotherapy.

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“…In contrast to CD134 and CD137, CD27 is expressed on naïve TC, BC, and NK cells and upregulated on activated TC, while CD70 is expressed on APC and activated TC [92]. Evidence for the role of CD27:CD70 in atherosclerosis is conflicting as ruptured atherosclerotic plaques expressed higher CD70 than those in stable lesions [93], and CD70 transgenic mice attenuated atherosclerotic development [94].…”

Section: Two-way Stimulatory Immune Checkpoint Induces Tissue and Sysmentioning

confidence: 99%

Metabolism-associated danger signal-induced immune response and reverse immune checkpoint-activated CD40+ monocyte differentiation

Dai

Saredy

et al. 2017

J Hematol Oncol

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Adaptive immunity is critical for disease progression and modulates T cell (TC) and antigen-presenting cell (APC) functions. Three signals were initially proposed for adaptive immune activation: signal 1 antigen recognition, signal 2 co-stimulation or co-inhibition, and signal 3 cytokine stimulation. In this article, we propose to term signal 2 as an immune checkpoint, which describes interactions of paired molecules leading to stimulation (stimulatory immune checkpoint) or inhibition (inhibitory immune checkpoint) of an immune response. We classify immune checkpoint into two categories: one-way immune checkpoint for forward signaling towards TC only, and two-way immune checkpoint for both forward and reverse signaling towards TC and APC, respectively. Recently, we and others provided evidence suggesting that metabolic risk factors (RF) activate innate and adaptive immunity, involving the induction of immune checkpoint molecules. We summarize these findings and suggest a novel theory, metabolism-associated danger signal (MADS) recognition, by which metabolic RF activate innate and adaptive immunity. We emphasize that MADS activates the reverse immune checkpoint which leads to APC inflammation in innate and adaptive immunity. Our recent evidence is shown that metabolic RF, such as uremic toxin or hyperhomocysteinemia, induced immune checkpoint molecule CD40 expression in monocytes (MC) and elevated serum soluble CD40 ligand (sCD40L) resulting in CD40+ MC differentiation. We propose that CD40+ MC is a novel pro-inflammatory MC subset and a reliable biomarker for chronic kidney disease severity. We summarize that CD40:CD40L immune checkpoint can induce TC and APC activation via forward stimulatory, reverse stimulatory, and TC contact-independent immune checkpoints. Finally, we modeled metabolic RF-induced two-way stimulatory immune checkpoint amplification and discussed potential signaling pathways including AP-1, NF-κB, NFAT, STAT, and DNA methylation and their contribution to systemic and tissue inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0504-1) contains supplementary material, which is available to authorized users.

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Targeting the T-Cell Co-stimulatory CD27/CD70 Pathway in Cancer Immunotherapy: Rationale and Potential

Cited by 130 publications

References 84 publications

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

CD27 stimulation unveils the efficacy of linked class I/II peptide vaccines in poorly immunogenic tumors by orchestrating a coordinated CD4/CD8 T cell response

Metabolism-associated danger signal-induced immune response and reverse immune checkpoint-activated CD40+ monocyte differentiation

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