CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses

Cheng, Hung‐Wei; Onder, Lucas; Cupovic, Jovana; Boesch, Maximilian; Novković, Mario; Pikor, Natalia; Tarantino, Ignazio; Rodriguez, Regulo; Schneider, Tino; Jochum, Wolfram; Brutsche, Martin; Ludewig, Burkhard

doi:10.1016/j.jaci.2017.12.998

Cited by 74 publications

(54 citation statements)

References 60 publications

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“…Cre × iDTR mouse model, as previously described (15,64). CCL19-Cre × Rosa26-EYFP reporter mice were generated by crossing the CCL19-Cre line with Rosa26-enhanced yellow fluorescent protein (EYFP) mice, which allowed for the identification of FRCs as well as their depletion, through the addition of the DTR gene (15).…”

Section: Discussionmentioning

confidence: 99%

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Maarouf¹,

Uehara²,

Kasinath³

et al. 2018

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Maarouf¹,

Uehara²,

Kasinath³

et al. 2018

JCI Insight

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“…Moreover, the anergic tumor endothelium lacks adhesion molecules such as ICAM and VCAM 11 , and therefore represents one of the substantial rate-limiting barriers restraining anti-cancer immunity [12][13][14] . Third, the scarcely expressed recruiting signals of lymphocytes in IET, such as CCL19, CCL21, CXCL9, and CXCL10, have delayed the infiltration of CTLs [15][16][17][18][19] . Given the biophysical features of IET, obstacles that stop CTLs from infiltrating could be classified as "physical obstacles" which includes CAFs, ECM and defect tumor vasculatures, and "signal deficiency" which means the lack of recruiting cytokines.…”

mentioning

confidence: 99%

Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors

et al. 2020

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The failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dualmechanism based CTLs infiltration enhancer, Nano-sapper, which can simultaneously reduce the physical obstacles in tumor microenvironment and recruiting CTLs to potentiate immunotherapy in IET. Nano-sapper consists a core that co-loaded with antifibrotic phosphatesmodified α-mangostin and plasmid encoding immune-enhanced cytokine LIGHT. Through reversing the abnormal activated fibroblasts, decreasing collagen deposition, normalizing the intratumoral vasculatures, and in situ stimulating the lymphocyte-recruiting chemoattractants expression, Nano-sapper paves the road for the CTLs infiltration, induces the intratumoral tertiary lymphoid structures, thus reshapes tumor microenvironment and potentiates checkpoint inhibitor against IET. This study demonstrates that the combination of antifibrotic agent and immune-enhanced cytokine might represent a modality in promoting immunotherapy against IET.

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“…Both CCL21, produced by high endothelial venules, lymphatic endothelial cells, and intranodal fibroblastic reticular cells, and CCL19, secreted by fibroblastic reticular cells within the lymph nodes, recruit T cells and T reg cells, B cells, and mature DCs to initial lymphatics and lymph nodes to elicit immune response [213]. Therefore, it is not surprising that the vast majority of DCs found in the tumor microenvironment are in their immature state and thus unable to trigger immune responses.…”

Section: Chemokines and Tumor Immunitymentioning

confidence: 99%

Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

Marcuzzi

Angioni

Molon

et al. 2018

IJMS

135

104

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Metastasis still represents the primary cause of cancer morbidity and mortality worldwide. Chemokine signalling contributes to the overall process of cancer growth and metastasis, and their expression in both primary tumors and metastatic lesions correlate with prognosis. Chemokines promote tumor metastasization by directly supporting cancer cell survival and invasion, angiogenesis, and by indirectly shaping the pre-metastatic niches and antitumor immunity. Here, we will focus on the relevant chemokine/chemokine receptor axes that have been described to drive the metastatic process. We elaborate on their role in the regulation of tumor angiogenesis and immune cell recruitment at both the primary tumor lesions and the pre-metastatic foci. Furthermore, we also discuss the advantages and limits of current pharmacological strategies developed to target chemokine networks for cancer therapy.

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CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses

Abstract: These data suggest that a distinct population of CCL19-producing FSCs fosters the development of an immune-stimulating intratumoral niche for immune cells to control cancer growth.

Cited by 74 publications

References 60 publications

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors

Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

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