Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma

Abstract

There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines (UN-SCC679 and UN-SCC680) derived from an N-nitroso-tris-chloroethylurea (NTCU) chemically-induced mouse model in A/J mice. Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classical LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the human LUSC organotropism to the brain, bones, liver and adrenal glands. In summary, we have generated a very valuable cell line tools for LUSC research that recapitulates the complexity of the human disease.

Potent clinical predictive and systemic adjuvant therapeutic value of plasma fractalkine in PD-L1/PD-1 blockade immunotherapy for lung cancer

“…All together, these results suggested that even though plasma soluble FKN may not have prognostic value in LUSC patients, a therapeutic role for this cytokine could not be discarded. UN-SCC680-derived tumors were highly sensitive to PD-1 blockade monotherapies, as previously reported 49 . Hence, only moderate synergy with FKN expression was observed ( Fig.…”

“…Importantly, we demonstrated that secreted FKN rendered 3LL LUAD-derived tumors sensitive to PD-1 blockade, a model highly refractory to PD-L1/PD-1 monotherapies 62 . We observed similar results for UN-SCC680 LUSC-derived tumors, although in this case PD-1 blockade had significant therapeutic effects on its own 49 . We concluded that although FKN plasma levels had differing prognostic value in LUAD and LUSC, the therapeutic use of FKN was not altered by tumor histology in mouse lung cancer models.…”

“…To further elucidate the effect of FKN in tumors with different histological origins, we engineered the murine adenocarcinoma cell line Lacun3 48 and two squamous lung cancer cell lines, UN-SCC679 and UN-SCC680 49 , to constitutively overexpress FKN ( Supplementary Fig. 5 ).…”

“…Cells were grown in DMEM (Gibco) supplemented with 10% FBS and 1% penicillin/streptomycin following standard procedures. The murine NTCU-induced lung squamous cell carcinoma cell lines Lacun-3, UN-SCC679 and UN-SCC680 are described elsewhere ( 50 ). 5 human lung adenocarcinoma cell lines (Calu6, H23, A549, HCC44, H358) and 5 human lung squamous carcinoma cell lines (H520, H1703, H226, H2170, SW900) were obtained from the American Type Culture Collection and grown following standard procedures.…”

Targeting Glutamine Metabolism to Enhance Immunoprevention of EGFR‐Driven Lung Cancer

“…In this model, wildtype A/J mice were given a total of four weekly EVax treatments (Figure 1D ). 1 week after completion of the four vaccines, UN‐SSC680 tumor cells [ 12 ] over‐expressing mutant EGFR L858R protein (UN‐SCC680 L858R ) were subcutaneously inoculated into the abdomens of vaccinated mice, and JHU083 oral gavage treatment was initiated. Upon termination of the study, we found that treatment with EVax or JHU083 alone significantly decreased tumor sizes by 38% and 42%, respectively (Figure 1E ).…”