CXCR3/CXCR3 Ligand Biological Axis Impairs RENCA Tumor Growth by a Mechanism of Immunoangiostasis

Pan, Judong; Burdick, Marie D.; Belperio, John A.; Xue, Ying; Gérard, Craig; Sharma, Sherven; Dubinett, Steven M.; Strieter, Robert M.

doi:10.1096/fasebj.20.4.a218-d

Cited by 3 publications

(3 citation statements)

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“…Our results showing a significant delay in tumor relapse after microparticle-delivered rCxcl9 are consistent with the anti-tumor effect of Cxcr3 ligands seen in previous studies (19)(20)(21).…”

Section: Discussionsupporting

confidence: 92%

Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma

Romano

Paradiso

Miller

et al. 2022

Preprint

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BRAF-mutant melanoma patients show significant responses to combined BRAF and MEK inhibition, but most patients relapse within 2 years. A major reservoir for such drug resistance is minimal residual disease (MRD), which is comprised of drug-tolerant tumor cells laying in a dormant state. Towards exploiting potential therapeutic vulnerabilities of MRD, we established a genetically engineered mouse model of BrafV600E-driven melanoma MRD wherein genetic BrafV600E extinction leads to strong but incomplete tumor regression. Transcriptional timecourse analysis of tumors after BrafV600E extinction revealed that after an initial surge of immune activation, tumors later became immunologically "cold" after MRD establishment, suggesting an immune-suppressive/evasive phenotype. Computational analysis identified candidate T-cell recruiting chemokines that may be central players in the process, being strongly upregulated initially and then steeply decreasing as the immune response faded. As a result, we hypothesized that sustaining the chemokine signaling could impair MRD maintenance through increased recruitment of effector T-cells. We show that intratumoral administration of recombinant Cxcl9, either naked or loaded in microparticles, significantly impaired the relapse of MRD in BRAF45 inhibited tumors. Our experiments constitute a proof of concept that chemokine-based microparticle delivery systems are a potential strategy to forestall tumor relapse and thus improve the clinical success of frontline treatment methods.

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Section: Discussionsupporting

confidence: 92%

Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma

Romano

Paradiso

Miller

et al. 2022

Preprint

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“…Strieter and colleagues proposed an interesting therapeutic model that combined systemic IL-2 with an intratumor CXCR3 ligand (CXCL9). In a mouse model, this immuno-cocktail led to significant reduction in tumor growth and angiogenesis, increased tumor necrosis, and enhanced intratumor infiltration of CXCR3+ mononuclear cells (119).…”

Section: Cancermentioning

confidence: 96%

Chemokines: coded messages for T-cell missions

Viola

Molon²,

Contento

2008

Front Biosci

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Chemokines and their receptors control leukocyte migration and homing throughout the body in both physiological and pathological conditions. In the context of the adaptive immune system, which requires high efficiency and control, chemokines and chemokine receptors represent a versatile code that orchestrates the "who, where and when" of the immune response by providing the spatio-temporal guidance for T-cell development, priming and effector functions. In addition to their chemotactic properties, chemokines can directly modulate T-cell responses by amplifying signals at the immune synapse and tuning Th1/Th2 polarization. In this review we will discuss the role of chemokines in T-cell biology, following an ideal pilgrimage that spans the key steps of the T-cell life.

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“…Chemokines and their receptors are important in directing metastatic tumor cells from the primary tumor to metastatic sites and are also essential in the migration of monocytes from the bloodstream to the metastatic niche to facilitate colonization 82‐84 . More specifically, in RCC, the chemokine CXCL12 and its receptor CXCR4 are regulated by the von Hippel‐Lindau/hypoxia‐inducible factor axis and have been identified as important prognostic factors 85,86 .…”

Section: Systemic Therapymentioning

confidence: 99%

An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma

Hasanov

Yeboa

Tucker

et al. 2022

CA A Cancer J Clinicians

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Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.

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CXCR3/CXCR3 Ligand Biological Axis Impairs RENCA Tumor Growth by a Mechanism of Immunoangiostasis

Cited by 3 publications

References 0 publications

Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma

Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma

Chemokines: coded messages for T-cell missions

An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma

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