Journal: Translational Oncology

Article Title: Circulating low-density neutrophils as biomarkers of resistance to first-line anti-PD-1/PD-L1 immunotherapy in non-small cell lung cancer

doi: 10.1016/j.tranon.2026.102755

Figure Lengend Snippet: Tumor growth kinetics following anti–PD-1, chemotherapy, and anti-Gr1 treatment in LLC tumor–bearing mice. (A): Diagram representing the therapeutic scheme followed for the in vivo experiment. LLC cells were injected subcutaneously on day 0 to establish tumours. Treatments were administered intraperitoneally on days 11, 14, and 17 after tumor cell inoculation, with anti-GR1 administered one day prior to each treatment cycle. The therapeutic regimens included anti-PD1 (100 μg/mouse), anti-GR1 (200 μg/mouse), and chemotherapy consisting of cisplatin (3 mg/kg) plus pemetrexed (100 mg/kg). (B): Growth curves of LLC cells subcutaneously injected into immunocompetent mice, comparing tumour volumes between control and (B) anti-PD-1 treatment, (C) anti-Gr1 treatment, (D) chemotherapy consisting on cisplatin plus pemetrexed, plus anti-PD-1 treatment, (E) chemotherapy plus anti-PD-1 plus anti-Gr1 treatment. *: p <0.05; ***: p <0.001; ****: p <0.0001.

Article Snippet: For the murine experiments, LLC cells were obtained from ATCC (#CRL-1642); anti-mouse Gr1 antibody (#BE0075, clone RB6-8C5) and anti-PD-1 antibody (#BE0273, clone RMP1-14) were purchased from BioXCell; pemetrexed (1000 mg/40 mL, 25 mg/mL) was obtained from TEVA; and cisplatin (#232120) was purchased from Sigma-Aldrich.

Techniques: In Vivo, Injection, Control

Journal: Cancer Discovery

Article Title: PD-1 Blockade–Induced DKK1 Expression by CD8 + T Cells Promotes Blood–Brain Barrier Permeabilization

doi: 10.1158/2159-8290.CD-25-1222

Figure Lengend Snippet: Induction with anti–PD-1 antibody prior to cisplatin chemotherapy increases the intracranial therapeutic efficacy. A, A schematic illustration depicting various treatment groups and their therapeutic regimens, evaluating the efficacy of anti–PD-1 and cisplatin-based combination therapy sequences on experimental BrM of anti-PD-1–resistant LLC cells. B, An experimental BrM assay was performed on 8-week-old C57BL/6 mice treated with anti–PD-1 and cisplatin chemotherapy in opposing sequences. A Kaplan–Meier survival curve is plotted ( n = 6–7 mice/group). C–E, Eight-week-old C57BL/6 mice harboring subcutaneous LLC xenografts (∼100 mm 3 ) were treated with IgG, anti–PD-1, IgG + cisplatin, anti–PD-1 + cisplatin, and the opposing sequence, cisplatin + anti–PD-1, and the therapeutic response was monitored. Tumor growth across various treatment groups is plotted (Arrow indicates start of the treatment; n = 4–5 mice/group; C ). A bar graph showing the activation status of CD8 + T cells isolated from the spleens of these mice is plotted, as assessed by flow cytometry ( D ). A bar graph showing the percentage of dead cells [propidium iodide (PI)–positive] in a tumor cell killing assay, using CD8 + T cells isolated from the spleens of mice from the different conditions cocultured with LLC cells, as assessed by flow cytometry ( E ). F and G, Adoptive transfer of wild-type (Vector) and DKK1 KD [guide RNA (gRNA)] CD8 + T cells obtained from BALB/c mice was performed on 8-week-old SCID mice subjected to an experimental BrM assay using the 4T1 cancer cells. These mice were subsequently treated with a combination sequence of anti–PD-1 and cisplatin. An illustration depicting the experimental methodology for testing the effect of DKK1 KD on the therapeutic efficacy of the anti–PD-1 + cisplatin combination sequence is provided. Kaplan–Meier survival curve is plotted ( n = 6 mice/group; G ). H, Eight-week-old BALB/c mice, preconditioned with a single dose of IgG/anti–PD-1 or untreated (naïve), received cisplatin monotherapy 72 hours later. After 6 hours, the brains were harvested and prepared for the assessment of cisplatin concentration using LC/MS. A bar graph showing absolute quantification of cisplatin in the brains of BALB/c mice from various treatment groups is plotted ( n = 3–4 mice/group). Significance was assessed by means of the log-rank test for B and G , two-way ANOVA for C , and one-way ANOVA for D , E , and H . *, P < 0.05; **, P < 0.01; ***, P < 0.001. [ A, Created in BioRender. Raviv, Z. (2026) https://BioRender.com/rezdwrc ; F, Created in BioRender. Raviv, Z. (2026) https://BioRender.com/oo7uvma .]

Article Snippet: Murine EMT6 (cat. #CRL-2755; RRID:CVCL_1923), 4T1 (cat. #CRL-2539; RRID:CVCL_0125) mammary carcinoma, and LLC (cat. #CRL-1642; RRID:CVCL_4358) cell lines were purchased from the ATCC.

Techniques: Drug discovery, Sequencing, Clinical Proteomics, Activation Assay, Isolation, Flow Cytometry, Adoptive Transfer Assay, Plasmid Preparation, Concentration Assay, Liquid Chromatography with Mass Spectroscopy, Quantitative Proteomics