Journal: Frontiers in Immunology

Article Title: Multimodal reprogramming of the tumor microenvironment by MMR and dual checkpoint blockade in hepatocellular carcinoma models

doi: 10.3389/fimmu.2025.1679665

Figure Lengend Snippet: Trivalent measles, mumps, and rubella vaccine (MMR) shows no systemic toxicity. (A) To assess MMR-related toxicities, naïve non-tumor-bearing mice were treated with an intrahepatic injection of MMR (1 × 10 2 TCID 50 ) or PBS. Plasma was collected at 24 h to assess markers of liver toxicity, nephrotoxicity, and electrolytes. (B) At 24 h post-treatment, body weights were not altered by intrahepatic MMR. Plasma markers of organ toxicity—albumin ( C , ALB), alkaline phosphatase ( D , ALP), alanine aminotransferase ( E , ALT), amylase ( F , AMY), total bilirubin ( G , TBIL), blood urea nitrogen ( H , BUN), calcium ( I , CA+), Potassium ( J , K+), and creatinine ( K , CRE)—were not altered by intrahepatic MMR.

Article Snippet: To prepare the vaccine for animal studies, lyophilized MMR vaccine powder vials were reconstituted and diluted with the provided diluents as recommended by the manufacturer (Merck).

Techniques: Injection, Clinical Proteomics

Journal: Frontiers in Immunology

Article Title: Multimodal reprogramming of the tumor microenvironment by MMR and dual checkpoint blockade in hepatocellular carcinoma models

doi: 10.3389/fimmu.2025.1679665

Figure Lengend Snippet: Trivalent measles, mumps, and rubella vaccine (MMR) did not affect blood cell counts and did not damage tissues. To assess MMR-related toxicities, naïve non-tumor-bearing mice were treated with an intrahepatic injection of MMR (1 × 10 2 TCID 50 ) or PBS. Blood cell counts were obtained at baseline (i.e., before intrahepatic injection; day 0) and on days 1, 7, and 21. Brain and liver tissues were harvested at the end of the experiment (21 days post-injection) and were stained and prepared for pathology analysis. (A-G) .

Article Snippet: To prepare the vaccine for animal studies, lyophilized MMR vaccine powder vials were reconstituted and diluted with the provided diluents as recommended by the manufacturer (Merck).

Techniques: Injection, Staining

Journal: Frontiers in Immunology

Article Title: Multimodal reprogramming of the tumor microenvironment by MMR and dual checkpoint blockade in hepatocellular carcinoma models

doi: 10.3389/fimmu.2025.1679665

Figure Lengend Snippet: Anti-tumor activity of vaccines for individual measles (MeV), mumps (MuV), and rubella (RuV) viruses and of the trivalent vaccine (MMR) in murine HCC Hepa 1–6 model. (A) Hepa 1–6 tumors treated with 3 intratumoral doses (1 weekly dose for 3 weeks) of MeV, MuV, RuV, MMR (1 × 10 2 TCID 50 per mouse), or PBS (n = 7/group). (B) Survival (shown as Kaplan-Meier curves) was monitored. (C-H) Hepa1–6 cells grown in culture were treated with MMR or individual viruses (MeV, MuV, or RuV) for 48 h before RNA extraction and qPCR amplification to characterize MHC class I and β-2-microglobulin (B2M) expression. (C, D) Expression of classical murine MHC class I (H2Kb, H2Db), (E) B2M, and (F-H) transporter associated with antigen-processing (TAP 1/2 and Tapbp) complex.

Article Snippet: To prepare the vaccine for animal studies, lyophilized MMR vaccine powder vials were reconstituted and diluted with the provided diluents as recommended by the manufacturer (Merck).

Techniques: Activity Assay, Vaccines, RNA Extraction, Amplification, Expressing

Journal: Frontiers in Immunology

Article Title: Multimodal reprogramming of the tumor microenvironment by MMR and dual checkpoint blockade in hepatocellular carcinoma models

doi: 10.3389/fimmu.2025.1679665

Figure Lengend Snippet: Trivalent measles, mumps, and rubella vaccine (MMR) combined with anti-PD-1 and anti-CTLA-4 prolongs survival in the murine R1LWT HCC subcutaneous (SQ) model. We investigated the anti-tumor effects of combining MMR with immune checkpoint blockade (ICB) in an immunocompetent HCC SQ mouse model (R1LWT). (A) We treated tumor-bearing female C57BL/6J mice with a weekly intratumoral injection of MMR (1 × 10 2 TCID 50 ) with or without ICB (intraperitoneal injections of anti-PD-1 and anti-CTLA4 antibodies; twice per week) for 3 weeks. (B) Survival was monitored. (C) shows a rechallenge result where all R1LWT-cured mice and naïve control mice were (re)challenged with SQ injection of R1LWT cells.

Article Snippet: To prepare the vaccine for animal studies, lyophilized MMR vaccine powder vials were reconstituted and diluted with the provided diluents as recommended by the manufacturer (Merck).

Techniques: Injection, Control

Journal: Frontiers in Immunology

Article Title: Multimodal reprogramming of the tumor microenvironment by MMR and dual checkpoint blockade in hepatocellular carcinoma models

doi: 10.3389/fimmu.2025.1679665

Figure Lengend Snippet: Trivalent measles, mumps, and rubella vaccine (MMR) in combination with antibodies that target PD-1 and CTLA-4 signaling enhances infiltration of cytotoxic T lymphocytes in R1LWT tumors. (A) Female C57BL6/J mice were implanted with R1LWT cells (n = 7/group). When the average tumor volume reached 80−120 mm 3 , PBS or MMR (1 × 10 2 TCID 50 ) was injected intratumorally on days 0, 7, and 14 with or without addition of immune checkpoint blockade (intraperitoneal injection of anti-PD-1 and anti-CTLA4 antibodies; twice per week, for 3 weeks). (B) Tumor volume was recorded weekly. Tumors were harvested at the end of the study for downstream analysis. (C) We used flow cytometry to analyze the effects on immune cell infiltration into the tumor microenvironment. (D-I) show levels of tumor immune infiltration (such as CD8+, PD-1+ CD44+) in ICB and the combined treatment groups.

Article Snippet: To prepare the vaccine for animal studies, lyophilized MMR vaccine powder vials were reconstituted and diluted with the provided diluents as recommended by the manufacturer (Merck).

Techniques: Injection, Flow Cytometry