Elimination of fluorescent protein immunogenicity permits modeling of metastasis in immune-competent settings

Grzelak, Candice Alexandra; Goddard, Erica T.; Lederer, Emma; Rajaram, Kamya; Dai, Jinxiang; Shor, Ryann E; Lim, Andrea R.; Kim, Jeanna; Beronja, Slobodan; Funnell, Alister P. W.; Ghajar, Cyrus M.

doi:10.1016/j.ccell.2021.11.004

Cited by 51 publications

(33 citation statements)

References 11 publications

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“…The rejection of tumors in the colon indicates increased immune surveillance compared to liver and sub-cutaneous tumors. This is in line with recently reported restrained primary tumor growth and metastasis as a result of increased immunogenicity against GFP in breast cancer metastasis models [ 60 ].…”

Section: Discussionsupporting

confidence: 91%

Modeling Colorectal Cancer Progression Reveals Niche-Dependent Clonal Selection

Vaquero-Siguero

Schleußner

Volk

et al. 2022

Cancers

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Colorectal cancer (CRC) is among the deadliest cancers worldwide, with metastasis being the main cause of patient mortality. During CRC progression the complex tumor ecosystem changes in its composition at virtually every stage. However, clonal dynamics and associated niche-dependencies at these stages are unknown. Hence, it is of importance to utilize models that faithfully recapitulate human CRC to define its clonal dynamics. We used an optical barcoding approach in mouse-derived organoids (MDOs) that revealed niche-dependent clonal selection. Our findings highlight that clonal selection is controlled by a site-specific niche, which critically contributes to cancer heterogeneity and has implications for therapeutic intervention.

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Section: Discussionsupporting

confidence: 91%

Modeling Colorectal Cancer Progression Reveals Niche-Dependent Clonal Selection

Vaquero-Siguero

Schleußner

Volk

et al. 2022

Cancers

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“…DNA barcoding technology that allows isolation of single clones to study if their phenotypes were acquired or pre-existent upon a specific bottleneck [128] Intravital imaging Assess cell state directly in the metastatic niche [121,[129][130][131] Fluorescence-activated cell sorting Assess marker expression defining a specific cell state [13] Optical barcoding system Isolate single clones on the base of 31 distinct fluorescent reporters to capture heterogeneity [83] Mouse models and cell lines Lgr5CreER/ Kras LSL-G12D /p53 fl/fl / Rosa26-YFP +/+ Mouse model of skin squamous cell carcinoma that generates skin tumors undergoing spontaneous EMT [13] Lgr5CreER/Kras LSL-G12D /p53 fl/fl /Rosa26-Δ Np63-IRES-GFP Mouse model of skin squamous cell carcinoma where cancer cells are blocked in the early hybrid EMT cell state [132] Tnc-CreER T2 /MMTV-Flpo/RC:: FrePe/MMTV-PyMT mouse Lineage tracing of cells in the hybrid EMT cell state [18] Cdh2-CreER T2 /MMTV-Flpo/RC:: FrePe/MMTV-PyMT mouse Lineage tracing of cells that underwent full EMT [18] MMTV-PyMT; Cdh1 fl/fl Mouse model allowing Cre recombinase inducible deletion of the epithelial marker E-cadherin in vivo [25] Cx3cr1-GFP;CCR2-RFP GFP/RFP tolerized mice to model metastatic disease in an immuno-competent setting [133,134] Trends in Cell Biology…”

Section: Discussionmentioning

confidence: 99%

Phenotypic plasticity during metastatic colonization

Jehanno¹,

Vulin²,

Richina³

et al. 2022

Trends in Cell Biology

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“…One caveat of labeled cell models, such as those expressing luciferase, green fluorescent protein (GFP), or red fluorescent protein (RFP), is that the marker can in and of itself be immunogenic [ 50 , 51 ]. However, by repeated passaging of cells through immunocompetent mice, we have selected a subline of luciferase expressing cells that are not cleared by the immune system.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Luciferase Labeled, Syngeneic Murine Model of Ovarian Cancer

Russell

Lim

Peters

et al. 2022

Cancers

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Despite advances in surgery and targeted therapies, the prognosis for women with high-grade serous ovarian cancer remains poor. Moreover, unlike other cancers, immunotherapy has minimally impacted outcomes in patients with ovarian cancer. Progress in this regard has been hindered by the lack of relevant syngeneic ovarian cancer models to study tumor immunity and evaluate immunotherapies. To address this problem, we developed a luciferase labeled murine model of high-grade serous ovarian cancer, STOSE.M1 luc. We defined its growth characteristics, immune cell repertoire, and response to anti PD-L1 immunotherapy. As with human ovarian cancer, we demonstrated that this model is poorly sensitive to immune checkpoint modulators. By developing the STOSE.M1 luc model, it will be possible to probe the mechanisms underlying resistance to immunotherapies and evaluate new therapeutic approaches to treat ovarian cancer.

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Elimination of fluorescent protein immunogenicity permits modeling of metastasis in immune-competent settings

Cited by 51 publications

References 11 publications

Modeling Colorectal Cancer Progression Reveals Niche-Dependent Clonal Selection

Modeling Colorectal Cancer Progression Reveals Niche-Dependent Clonal Selection

Phenotypic plasticity during metastatic colonization

Development and Characterization of a Luciferase Labeled, Syngeneic Murine Model of Ovarian Cancer

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