Journal: Molecular Therapy Oncology

Article Title: Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy

doi: 10.1016/j.omton.2025.201109

Figure Lengend Snippet: MV-s-NAP-uPA + aPD-1 + aTIGIT + paroxetine combination increases S1P1 expression on BM lymphocytes in an orthotopic CT-2A/C57BL/6 mouse model (A) Schematic illustration of the treatment plan. (B) Median S1P1 staining in the BM lymphocytes 8 days post-CT-2A implantation. (C) Median S1P1 staining in the BM lymphocytes 13/14 days post-CT-2A implantation. (D) Median S1P1 staining in the CD4+ BM lymphocytes 13/14 days post-CT-2A implantation. (E) Median S1P1 staining in the CD8+ BM lymphocytes 13/14 days post-CT-2A implantation. (F) Median S1P1 staining in the NKT BM lymphocytes 13/14 days post-CT-2A implantation. The graphs represent the mean values obtained with flow cytometry analysis of the isolated tissue. Statistical analysis was conducted with a one-way ANOVA followed by Tukey’s multiple comparisons test, with 3–4 mice analyzed per group at each time point. p values less than 0.05 were considered significant.

Article Snippet: The antibodies used were the following: aPD-1 (anti-mPD-1-mIgG1e3, clone: RMP1-14, rat IgG2a,κ and features mouse IgG1e3 isotype-constant region; InvivoGen, San Diego, CA, CAT #mpd1-mab15-10) and aTIGIT (anti-mTIGIT-mIgG2a, clone: 10A7, hamster IgG2a and features the mIgG2a isotype-constant region; InvivoGen, San Diego, CA, CAT #mtigit-mab10-10).

Techniques: Expressing, Staining, Flow Cytometry, Isolation

Journal: Molecular Therapy Oncology

Article Title: Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy

doi: 10.1016/j.omton.2025.201109

Figure Lengend Snippet: Paroxetine mobilizes lymphocytes following treatment with MV-s-NAP-uPA oncolytic virotherapy and immunovirotherapy in an orthotopic CT-2A/C57BL/6 mouse model (A) Schematic illustration of the treatment plan. (B) Percentage of circulating lymphocytes among all immune cells in PBMCs on days 13 and 18 post-CT-2A implantation. (C) Standardized counts of CD4+ and CD8+ single-positive PBMCs following MV-s-NAP-uPA + aPD-1 + aTIGIT immunovirotherapy with and without paroxetine on day 13/14 post-CT-2A implantation. (D) Standardized counts of CD4+ and CD8+ single-positive PBMCs following MV-s-NAP-uPA oncolytic virotherapy with and without paroxetine on day 13/14 post-CT-2A implantation. (E) Comparison of thymus weights in mice reaching a predetermined sacrifice endpoint, evaluating the effects of paroxetine vs. respective controls. For (B–D), the graphs represent the mean values obtained with flow cytometry analysis of the isolated tissue. Statistical analysis was conducted with one-way ANOVA followed by Tukey’s multiple comparisons test, with 3–4 mice analyzed per group at each time point for (B–D) and 11–26 mice analyzed per group for (E). p values less than 0.05 were considered significant.

Article Snippet: The antibodies used were the following: aPD-1 (anti-mPD-1-mIgG1e3, clone: RMP1-14, rat IgG2a,κ and features mouse IgG1e3 isotype-constant region; InvivoGen, San Diego, CA, CAT #mpd1-mab15-10) and aTIGIT (anti-mTIGIT-mIgG2a, clone: 10A7, hamster IgG2a and features the mIgG2a isotype-constant region; InvivoGen, San Diego, CA, CAT #mtigit-mab10-10).

Techniques: Comparison, Flow Cytometry, Isolation

Journal: Molecular Therapy Oncology

Article Title: Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy

doi: 10.1016/j.omton.2025.201109

Figure Lengend Snippet: Paroxetine enhances lymphocyte activation in lymphoid organs and peripheral blood following treatment with MV-s-NAP-uPA + aPD-1 + aTIGIT immunovirotherapy in an orthotopic CT-2A/C57BL/6 mouse model (A) Schematic illustration of the treatment plan. (B) Percentage of CD69+ double-positive (CD4+CD8+) and single-positive helper T cells (CD4+) in the thymus of mice treated with immunovirotherapy with and without paroxetine on day 8 post-CT-2A implantation. (C–E) Percentage of CD25+/FOXP3− CD4+ cells in the thymus, spleen, and BM of mice treated with immunovirotherapy with and without paroxetine on day 8 post-CT-2A implantation. (F) Percentage of CD25+/FOXP3− CD8+ cells in the peripheral blood of mice treated with immunovirotherapy with and without paroxetine on days 8 and 13 post-CT-2A implantation. (G) Percentage of Tregs in the BM of mice treated with immunovirotherapy with and without paroxetine on day 18 post-CT-2A implantation. (H) Percentage of TIM-3+ lymphocytes in the thymus on day 18 post-CT-2A implantation. (I) Percentage of PD-1+ CD8+ cells in the spleen on day 18 post-CT-2A implantation. The graphs represent the mean values obtained with flow cytometry analysis of the isolated tissues. Statistical analysis was conducted with student two-tailed t tests with 3–4 mice analyzed per group at each time point. p values less than 0.05 were considered significant.

Article Snippet: The antibodies used were the following: aPD-1 (anti-mPD-1-mIgG1e3, clone: RMP1-14, rat IgG2a,κ and features mouse IgG1e3 isotype-constant region; InvivoGen, San Diego, CA, CAT #mpd1-mab15-10) and aTIGIT (anti-mTIGIT-mIgG2a, clone: 10A7, hamster IgG2a and features the mIgG2a isotype-constant region; InvivoGen, San Diego, CA, CAT #mtigit-mab10-10).

Techniques: Activation Assay, Flow Cytometry, Isolation, Two Tailed Test

Journal: Molecular Therapy Oncology

Article Title: Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy

doi: 10.1016/j.omton.2025.201109

Figure Lengend Snippet: The effect of paroxetine on the survival in an orthotopic CT-2A/C57BL/6 mouse model treated with MV-s-NAP-uPA + aPD-1 + aTIGIT immunovirotherapy (A) Schematic illustration of the treatment plan in the pilot survival mouse experiment. (B) Kaplan-Meier plot representing the survival in the pilot study evaluating the effect of paroxetine and/or G-CSF in combination with immunovirotherapy (n = 4–8 mice per group). (C) Schematic illustration of our rechallenge experiment. (D) Kaplan-Meier plot representing the survival following rechallenge of the surviving mice from each group 180 days after the original tumor implantation with the same CT-2A cell line or a foreign melanoma B16-F10 cell line (n = 3–4 mice per group). Mice were rechallenged with intracranial implantation. (E) Schematic illustration of the treatment plan for the survival experiment presented in F. (F) Kaplan-Meier plot representing the survival following treatment with paroxetine in combination with oncolytic virotherapy, immunotherapy, and immunovirotherapy (n = 6–17 mice per group). p values less than 0.05 were considered significant.

Article Snippet: The antibodies used were the following: aPD-1 (anti-mPD-1-mIgG1e3, clone: RMP1-14, rat IgG2a,κ and features mouse IgG1e3 isotype-constant region; InvivoGen, San Diego, CA, CAT #mpd1-mab15-10) and aTIGIT (anti-mTIGIT-mIgG2a, clone: 10A7, hamster IgG2a and features the mIgG2a isotype-constant region; InvivoGen, San Diego, CA, CAT #mtigit-mab10-10).

Techniques: Tumor Implantation

Journal: Molecular Therapy Oncology

Article Title: Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy

doi: 10.1016/j.omton.2025.201109

Figure Lengend Snippet: Combination therapy with MV-s-NAP-uPA + aPD-1 + aTIGIT + paroxetine does not increase toxicity in the orthotopic CT-2A/C57BL/6 mouse model (A) Mice from the survival studies were weighed every 3–4 days, and the percent change from baseline is presented longitudinally. Except for a brief post-operative weight loss, which was consistent across vehicle-treated mice and those receiving combinations based on MV-s-NAP-uPA, all treated mice, regardless of their treatment groups, gained weight at a comparable rate. (B) Cytokine analysis for IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, IFN-γ, IL-12p70, GM-CSF, TNF-α, and IL-18 was performed on plasma samples collected from mice on days 8, 13/14, and 18/19 post-CT-2A implantation. The graphs in (B) represent the mean values obtained from 3–4 mice per group at each time point.

Article Snippet: The antibodies used were the following: aPD-1 (anti-mPD-1-mIgG1e3, clone: RMP1-14, rat IgG2a,κ and features mouse IgG1e3 isotype-constant region; InvivoGen, San Diego, CA, CAT #mpd1-mab15-10) and aTIGIT (anti-mTIGIT-mIgG2a, clone: 10A7, hamster IgG2a and features the mIgG2a isotype-constant region; InvivoGen, San Diego, CA, CAT #mtigit-mab10-10).

Techniques: Clinical Proteomics

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: ( a ) Splenocytes from Ifng YFP/YFP Apoe − / − mice were stimulated with PMA/ionomycin with Brefeldin A for 4 hr and analyzed for IFN-γ-YFP and IFN-γ-AF700 expression. ( b-d ) Ifng YFP/YFP Apoe − / − mice were fed a high-cholesterol diet for 12 weeks, and flow cytometry was performed to characterize IFN-γ-producing T cells (n = 11). ( b ) Increased frequency of IFN-γ-YFP expression in Tbet + splenic CD4 (**** p = 6.9E-5) and CD8 T cells (*** p = 0.0004) compared to Tbet − T cells. ( c ) Overlay flow cytometry plots of IFN-γ + (orange) and IFN-γ − (grey) aortic CD4 and CD8 T cells. ( d ) Flow cytometry plots of PD1-PE/Dazzle antibody staining and matched controls, PE/Dazzle-rat IgG2a isotype control (PD1 isotype) and PD1-PE/Dazzle fluorescent minus-one (FMO), of splenic CD4 T cells. ( e ) Representative immunohistochemical staining of PDL1 in aortic root cross-section of Ifng YFP/YFP Apoe − / − mice fed a high-cholesterol diet for 16 weeks (n = 4). ( b ) Bars denote median, analyzed with two-sided Mann-Whitney U test.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Expressing, Flow Cytometry, Staining, Control, Immunohistochemical staining, MANN-WHITNEY

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: a – c , TCR signaling reporter mice ( Nur77 wt/GFP Apoe − / − ) were generated and fed an HCD for 12 weeks, and, at euthanization, T cell phenotype was analyzed ( n = 9). a , Flow cytometry plots of Nur77–GFP expression on aortic T cells. b , MFI of Slamf6 (** P = 0.004), PD-1 (** P = 0.0019) and Tim3 (*** P = 0.0002) of Nur77 − and Nur77 + (recent TCR activation) aortic CD4. c , MFI of Slamf6 (**** P = 9.2 × 10 −5 ), PD-1 and Tim3 (* P = 0.01) of Nur77 − and Nur77 + aortic CD8 T cells. d , Flow cytometry plots of CD69 and CD103 expression on aortic CD8 T cells of Ifng YFP/YFP Apoe − / − mice fed an HCD for 14 weeks ( n = 9). e , f , Quantification of percent CD69 + T cells (CD4 **** P = 8.5 × 10 −5 , * P = 0.049; CD8 **** P = 5.6 × 10 −9 , *** P = 0.0004) and CD69 + CD103 + T cells (CD4 * P = 0.012, CD8 * P = 0.011) within PD-1 subsets in the aorta. g , h , Flow cytometry analyzing CD69 and Nur77–GFP expression within PD-1 subsets of aortic CD4 T cells from Ifng YFP/YFP Nur7 wt/GFP Apoe − / − mice fed an HCD for 10 weeks ( n = 6). Quantification of non-activated CD4 T RM -like cells (CD69 + Nur77–GFP − ) and recently activated CD4 T cells (CD69 − Nur77–GFP + and CD69 + Nur77–GFP + ). i – j , Flow cytometry analyzing CD69 and Nur77–GFP expression within PD-1 subsets of aortic CD8 T cells. k – m , In a separate cohort, Ifng YFP/YFP Apoe − / − mice were fed an HCD for 10 weeks before receiving intraperitoneal injections of anti-IL-2 antibodies or control IgG ( n = 9 per group) for 2 weeks. k , l , Flow cytometric analysis of aortic memory T cells to assess composition of PD-1 subsets and subsets of cells expressing Slamf6 and/or Tim3. m , Flow cytometric analysis of IFNγ production by aortic CD44 + CD4 and CD44 + CD8 T cells. b , l , Bars denote median, analyzed with two-sided Mann–Whitney U -test. c , m , Bars denote mean, analyzed with two-sided unpaired t -test. e , f , h , j , Bars denote median, analyzed with two-sided Kruskal–Wallis test. h , j , P values compared to PD-1 − subset (CD4 PD-1 int ** P = 0.0088, CD4 PD-1 high * P = 0.0016, CD8 PD-1 int * P = 0.031, CD8 PD-1 high *** P = 0.0005). act, activated; Ctrl, control.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Generated, Flow Cytometry, Expressing, Activation Assay, Control, MANN-WHITNEY

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: ( a - c ) Atherosclerotic dual-reporter mice ( Ifng YFP/YFP Nur77 wt/GFP Apoe − / − ) were generated, fed a high-cholesterol diet for 10 weeks, and flow cytometry was performed to characterize Nur77 expression on IFN-γ-producing T cells in spleen, iliac aortic-draining lymph node (aLN), and aorta (n = 6). ( a ) Flow cytometry plots and ( b-c ) quantification of association between Nur77-GFP expression and PD1 expression within IFN-γ-YFP + CD4 and CD8 T cells in the aorta, iliac aortic-draining lymph nodes (aLN), and spleen. ( d ) Representative flow cytometry gating for identifying follicular T helper cells (Tfh; CXC5 + PD1 high CD4 + ) in Ifng YFP/YFP Apoe − / − mice. ( e ) Experimental design for anti-IL-2 study. Ifng YFP/YFP Apoe − / − mice were fed a high cholesterol diet (HCD) for 10 weeks before receiving i.p . injections (3 doses, 5 days apart) of anti-IL-2 antibodies or control IgG (n = 9/group) for 2 weeks.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Generated, Flow Cytometry, Expressing, Control

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: a – k , o – u , Ifng YFP/YFP Apoe − / − mice were fed an HCD for 10 weeks before administering biweekly intraperitoneal injections of a murine blocking anti-PD-1 antibody or isotype IgG control ( n = 12 per group). Mice received a total of 12 injections over 6 weeks and were euthanized after a total of 16 weeks of diet. b , Quantification of average plaque area of aortic subvalvular cross-sections. c , d , Quantification and representative immunohistochemical staining of T cells (CD3 + ) in aortic root plaques (**** P = 5 × 10 −5 ). e – i , Representative flow cytometry plots and quantification of frequency and numbers of PD-1 subsets of aortic memory CD4 (*** P = 0.0001) and CD8 ( h **** P = 7.4 × 10 −7 , i **** P = 5.2 × 10 −6 ) T cells. j , k , Flow cytometric analysis of frequency of Tim3 + PD-1 + memory CD4 and CD8 aortic T cells (** P = 0.0024) and frequency of IFNγ production of memory CD4 and CD8 aortic T cells (** P = 0.0023, 0.0022). l , m , Representative immunohistochemical images of and quantification of presence of at least one T cell foci in the plaque and/or surrounding adventitia (* P = 0.024). For study details of 3-week anti-PD-1 cohort, see Extended Data Fig. (ctrl IgG n = 12, anti-PD-1 n = 13). n , Impact of presence of tumor (MC38 tumor) during anti-PD-1 therapy ( n = 7 per group) on T cell (CD3 + ) infiltration into subvalvular aortic plaques (** P = 0.0079, * P = 0.026) compared to ctrl IgG ( n = 5 per group), determined by immunohistochemistry. o – q , Quantification and representative immunohistochemical staining of neutrophils (Ly6G + ) in aortic root plaques (** P = 0.0070) and adventitia (**** P = 9.5 × 10 −5 ) in Ifng YFP/YFP Apoe − / − mice treated with PD-1 blockade or isotype IgG ctrl for 6 weeks ( n = 12 per group). r , Quantification of immunohistochemical staining of macrophages (CD68 + ) in aortic root plaques. s , Gene expression analysis of aortic subvalvular cross-sections of ctrl IgG-treated or anti-PD-1-treated mice. Genes are reported as upregulated or downregulated in anti-PD-1-treated mouse compared to isotype IgG control. Adjusted P value is adjusted for FDR. t , u , Concentration of plasma cytokines CXCL9 (** P = 0.0063) and CXCL10 (* P = 0.037). b , c , i , n , p – r , u , Bars denote median, analyzed with two-sided Mann–Whitney U -test. t , Bars denote mean, analyzed with two-sided unpaired t -test. f – h , j , k , Bars denote median, analyzed with two-sided Mann–Whitney U -test or two-sided unpaired t -test. m , Analyzed with one-sided Fisher’s exact test. adj., adjusted; Adv., adventitia; Avg., average; ctrl, control; FC, fold change; i.p., intraperitoneal; w, week.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Blocking Assay, Control, Immunohistochemical staining, Staining, Flow Cytometry, Immunohistochemistry, Gene Expression, Concentration Assay, Clinical Proteomics, MANN-WHITNEY

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: Ifng YFP/YFP Apoe − / − mice were fed a high-cholesterol diet for 10 weeks before administration of bi-weekly i.p . injections of a murine blocking anti-PD1 antibody or isotype IgG control (n = 12/group) for 6 weeks. ( a ) Quantification of CD3 + cells in adventitia of aortic-root sections. Adventitia designated as 100 μm from smooth muscle layer of aortic valve. ( b ) Isotype IgG staining for CD3 immunohistochemical analysis of aortic root cross-sections. ( c ) Quantification of T cells (TCRβ + CD45 + ) per whole-aorta digest analyzed by flow cytometry (* p = 0.010). ( d-h ) In the short-term anti-PD1 cohort, Ifng YFP/YFP Apoe − / − mice were fed a high-cholesterol diet for 21 weeks before administration of bi-weekly i.p . injections of anti-PD1 antibody or isotype IgG control (n = 11-12/group). Mice received a total of six injections and were terminated after a total of 24 weeks of diet. ( e ) Average plaque area determined by Oil Red O staining of aortic subvalvular cross-sections. ( f-g ) Quantification and representative image of immunohistochemical analysis of CD3 + cells in aortic root plaques (*** p = 0.0002). ( h ) Representative immunohistochemical staining images and confocal images of CD3 and CD19 staining of advanced adventitial foci. ( i ) Measurements of MC38 tumor diameter in HCD-fed Ifng YFP/YFP Apoe − / − mice with (n = 5) and without (n = 7) PD1 blockade. Data presented as mean values +/- SD. ( j-k ) Representative images of immunohistochemical staining of neutrophils (Ly6G) and macrophages (CD68) in Ifng YFP/YFP Apoe − / − mice treated with PD1 blockade or isotype IgG control for 6 weeks (n = 12/group). ( l-p ) Concentration of plasma cytokines CCL4 (* p = 0.023), IL-6, TNF-α, IL-4 (*** p = 0.0009), and CCL2 (** p = 0.0013) in Ifng YFP/YFP Apoe − / − mice treated with anti-PD1 or isotype IgG control for 6 weeks. ( a , c , f , m - p ). Bars denote median, analyzed with two-sided Mann-Whitney U test. ( e, l ) Bars denote mean, analyzed with two-sided unpaired t test.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Blocking Assay, Control, Staining, Immunohistochemical staining, Flow Cytometry, Concentration Assay, Clinical Proteomics, MANN-WHITNEY

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: Ifng YFP/YFP Apoe − / − mice were fed with an HCD for 4 months and treated for the final 3 weeks with isotype control only ( n = 11), depleting anti-PD-1 (RMP1.30, n = 10) only, ctrl IgG for 1 week prior to injection of blocking anti-PD-1 antibodies (ctrl IgG + anti-PD-1, n = 13) or depleting anti-PD-1 (RMP1.30) for 1 week prior to injection of blocking anti-PD-1 antibodies (RMP1.30 + anti-PD-1, n = 13). a , Experimental overview. b , c , Numbers of circulating CD44 + PD-1 int CD4 and CD8 T cells throughout treatment course (days 0, 7 and 21). d , e , Numbers of circulating CD44 + PD-1 high CD4 (** P = 0.0010) and CD8 (** P = 0.0014, * P = 0.017) T cells throughout the treatment course. f , g , Quantification and representative immunohistochemical staining of T cells (CD3 + ) in aortic root plaques (** P = 0.0077, * P = 0.027). h , i , Flow cytometric analysis of counts of progenitor exhausted (CD44 + Slamf6 + Tim3 − PD-1 int ) aortic CD4 (* P = 0.025, ** P = 0.0072) and CD8 (*** P = 0.0004, * P = 0.014, 0.012) T cells. j , k , Flow cytometric analysis of counts CD44 + PD-1 high aortic CD4 (* P = 0.039, 0.011, 0.014) and CD8 (*** P = 0.009, 0.0021, **** P = 2.4 × 10 −6 ) T cells. l , m , Flow cytometric analysis of frequency of IFNγ production by aortic memory CD4 (*** P = 0.0006, ** P = 0.0013, * P = 0.014, 0.026) and CD8 (*** P = 0.0006, 0.0009, ** P = 0.0061, 0.0097) T cells. b – e , Data presented as mean values ± s.e.m., analyzed with mixed-effects multiple comparisons analysis. g – l , Bars denote median, analyzed with Kruskal–Wallis test. m , Bars denote mean, analyzed with one-way ANOVA. P values are reported top-to-bottom and left-to-right. ctrl, control.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Control, Injection, Blocking Assay, Immunohistochemical staining, Staining

Journal: Nature Cardiovascular Research

Article Title: Progenitor exhausted PD-1 + T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

doi: 10.1038/s44161-025-00713-2

Figure Lengend Snippet: Ifng YFP/YFP Apoe − / − mice fed HCD-fed for 4 months were treated in the final 3 weeks with either: isotype control only (n = 11), depleting anti-PD1 (RMP1.30, n = 10) only, ctrl IgG for one week prior to injection of blocking anti-PD1 antibodies (ctrl IgG + anti-PD1, n = 13), depleting anti-PD1 (RMP1.30) for one week prior to injection of blocking anti-PD1 antibodies (RMP1.30 + anti-PD1; n = 13). ( a-b ) Quantification of aortic CD44 + PD1 int CD4 (top-down, * p = 0.031, ** p = 0.0044, * p = 0.035) and CD44 + PD1 int CD8 (*** p = 0.0005, * p = 0.019, ** p = 0.0011, * p = 0.033) T cells. Bars denote median, analyzed with two-sided Kruskal-Wallis test.

Article Snippet: Mice were randomly assigned to receive intraperitoneal injections of either murinized and effector-less anti-PD-1 antibody (clone: RMP1-14, anti-mPD-1-mIgG1e3; InvivoGen, mpd1-mab15-50) or isotype control IgG2a (anti-mPD-1-mIgG1e3, InvivoFit; InvivoGen) biweekly for 6 weeks at 10 mg kg −1 ( n = 12 per group).

Techniques: Control, Injection, Blocking Assay