Supplementary Table S1. H-scores of ICAM-1, VCAM-1 and IP-10 expression in tumors of melanoma patients before and after ipilimumab or Ipi-Bev treatment.

Slides:

Advertisements

Similar presentations

Antoni Ribas, M.D., Ph.D. Professor of Medicine Professor of Surgery

Advertisements

SPH 247 Statistical Analysis of Laboratory Data 1April 16, 2013SPH 247 Statistical Analysis of Laboratory Data.

Enhancement Of T-Cell Immunity To Osteosarcoma By Modulation Of Programmed Death Receptor Pathway Pooja Hingorani, Danielle Lussier, Joseph Blattman.

Insert Program or Hospital Logo Introduction Melanoma is notoriously resistant to chemotherapy. While surgical resection and adjuvant chemotherapy can.

Maude et al. BLOOD, 25 JUNE 2015 x VOLUME 125, NUMBER 26

Phase II Trial of Ipilimumab Monotherapy in Melanoma Patients with Brain Metastases Lawrence DP et al. Proc ASCO 2010;Abstract 8523.

Pharmacogenetic analysis in metastatic colorectal cancer (mCRC) patients treated with second-line irinotecan (IR)+/- cetuximab (CB): The EPIC experience.

SERUM CYTOKINE EXPRESSION ACCORDING TO LAMIVUDINE THERAPY RESPONSE OF CHRONIC HEPATITIS B VIRUS INFECTION Jungyong Park 1, Younhee Park 1, Young Lan Kim.

MRD testing: which platforms, which patients?

Regulation of human cytokines by Cordyceps militaris

Training Set Clinicopathological parameters of the training set

TUMOR PD-L1 TIL PD-L1 TUMOR & TIL PD-L1 Age Low High P value R Pearson

Pembrolizumab Drugbank ID :DB09037 Half life : 28 days.

Supplementary Figure 1 Supplementary Figure 1: ROR agonists increase the expression of a luciferase reporter driven by Gal4-ROR. In HEK293T cells, Gal4-ROR

Fig 1A. Patient enrollment flow chart

Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients Aristea Sideri, Kyriaki Bakirtzi,

Suppl. Fig. 1 A B C No tumor - +

Combined Inhibition of PD-L1, MEK, and BRAF Active in Advanced Melanoma CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* May 29 -

The efficacy of Chinese herbal medicine as an adjunctive therapy for colorectal cancer: A systematic review and meta-analysis Linda L.D. Zhong, Hai-Yong.

Invest. Ophthalmol. Vis. Sci ;48(7): doi: /iovs Figure Legend:

Supplementary Table 1. (A) S100β Validation set (n=76 ER-positive and ER-negative patients). (B) S100β Validation set (n=59 ER-positive patients). Association.

Distinct baseline tissue biomarkers are associated with response to nivolumab and ipilimumab in melanoma: CheckMate 064 Scott J. Rodig,1,2 Daniel Gusenleitner,2.

MRD in Myeloma: the Future is Here

MicroRNAs for the Prediction of Early Response to Sorafenib Treatment in Human Hepatocellular Carcinoma Liver Cancer 2017;6: DOI: /

Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets by Kartik Sehgal,

Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients Stephany P. Monsanto, M.Sc.,

The role of viruses in acute exacerbations of asthma

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies

Supplementary Figure legends

The pro-inflammatory and chemotactic cytokine microenvironment of the abdominal aortic aneurysm wall: A protein array study Rachel K. Middleton, BSc,

Volume 20, Issue 1, Pages (January 2012)

Domenica 03 giugno Highlight a cura di Filippo de Marinis

Can Determination of Circulating Endothelial Cells and Serum Caspase-Cleaved CK18 Predict for Response and Survival in Patients with Advanced Non–Small-Cell.

Volume 140, Issue 2, Pages e4 (February 2011)

Response to Carfilzomib Therapy

Fig. 5. Serum VEGF-C correlates with antitumor immune responses and PFS after immunotherapy in human metastatic melanoma patients. Serum VEGF-C correlates.

BALB/c scid mice have higher levels of macrophage-stimulating cytokines in circulation compared with BALB/c control mice. BALB/c scid mice have higher.

Table S1: Characteristics of the cancer patients

BRAFV600E promotes glycolysis in melanoma cells via regulation of GLUT1, GLUT3, and HK2. BRAFV600E promotes glycolysis in melanoma cells via regulation.

Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma1 Phase 3 Randomized Study of Ipilimumab (IPI) plus Dacarbazine (DTIC) vs DTIC.

Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS by Takeshi Sugio, Kohta Miyawaki, Koji Kato, Kensuke Sasaki, Kyohei Yamada,

Volume 128, Issue 7, Pages (June 2005)

Supplementary Table 1. Summary of surface marker expression of adherent (A) and sphere-forming MRT cell lines (B), and primary tumors (C). A Sample CD146.

Figure 1 BG-12 treatment reduced total circulating B cells and had variable effects on memory B cells BG-12 treatment reduced total circulating B cells.

Supplementary Figure S1

Local injury of the endometrium induces an inflammatory response that promotes successful implantation Yulia Gnainsky, Ph.D., Irit Granot, Ph.D., Paulomi.

Figure 2 Effect of DMF therapy on the T helper cell repertoire and cytokine production Effect of DMF therapy on the T helper cell repertoire and cytokine.

Nat. Rev. Rheumatol. doi: /nrrheum

Acute nephrotoxic and obstructive injury primes the kidney to endotoxin-driven cytokine/chemokine production R.A. Zager, A.C.M. Johnson, S.Y. Hanson,

Figure S1. A. B. Figure S1. Kaplan-Meier curve of progression-free survival by treatment group in soluble heregulin (HRG)-high population (A) and soluble.

Clinical response to anti-ERBB3 mAb therapy in a patient with an advanced NRG1-rearranged non–small cell lung cancer. Clinical response to anti-ERBB3 mAb.

Effect of naïve or SCM percentage and cytokines on expansion potential

Pre- and post-vorinostat values of ER-related gene expression using the Oncotype DX 21-gene assay. Pre- and post-vorinostat values of ER-related gene expression.

Time to onset of hypothyroidism after first treatment with immune checkpoint inhibitors in the combination therapy and monotherapy groups. Time to onset.

MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma by Scott J. Rodig, Daniel Gusenleitner, Donald.

Kaplan–Meier curves for PFS and OS (for patients treated with anti-PD-1/PD-L1 monotherapy). Kaplan–Meier curves for PFS and OS (for patients treated with.

Linear correlationa between TMB cutoff for ORb for CR/PR rates and HRc for PFS, and OS depending on TMB for patients treated with anti-PD-1/PD-L1 monotherapy.

Effect of anti-cyCD79b (10D10) and anti-cyCD79b (10D10)-MCC-DM1 on cytokine levels in cynomolgus monkeys. Effect of anti-cyCD79b (10D10) and anti-cyCD79b.

Schematic model illustrating how paracrine signaling drives LPS-stimulated cytokine secretion. Schematic model illustrating how paracrine signaling drives.

Correlation of PTEN loss in melanoma cells with an immune resistance phenotype. Correlation of PTEN loss in melanoma cells with an immune resistance phenotype.

Tumor protection induced by therapeutic PLG vaccination in combination with blockade antibodies. Tumor protection induced by therapeutic PLG vaccination.

Increased frequency and number of KLL-specific clonotypes in tumors is associated with improved MCC-specific survival. Increased frequency and number of.

Genomic determinants of response to cytotoxic chemotherapy.

Antibody-mediated blockade of the immune-inhibitory PD-1–PD-L1 signaling pathway prolongs survival in poly(I:C)-treated mice. Antibody-mediated blockade.

ADU-S100 primes the innate immune system in tolerant, tumor bearing neu/N mice. ADU-S100 primes the innate immune system in tolerant, tumor bearing neu/N.

Survival, subsequent therapies, and response.

Biopsies of the vaccination site were obtained 48 h after the first vaccination. Biopsies of the vaccination site were obtained 48 h after the first vaccination.

TMEscore is a prognostic biomarker and predicts immunotherapeutic benefit. TMEscore is a prognostic biomarker and predicts immunotherapeutic benefit. A,

* OS >3yr with No Next Line * * * * *

Presentation transcript:

Supplementary Table S1. H-scores of ICAM-1, VCAM-1 and IP-10 expression in tumors of melanoma patients before and after ipilimumab or Ipi-Bev treatment. Treatment Patient Tumor ICAM-1 VCAM-1 IP-10 Cancer EC Ipi-Bev P1 Pre 140 180 Post 120 90 30 P4 270 210 80 100 P9 200 20 P20 240 50 P27 300 P28 160 60 150 P31 Ipilimumab 260 P2 70 P3 40 N/A 110 P5 P6 H-scores were calculated by multiplying the percentage of positive cells with their intensity (1, 2 or 3). Cases with concomitant upregulation of ICAM-1and VCAM-1 in EC and IP-10 in tumor cells were highlighted.

Supplementary Table S2. CXCR3 expression on circulating CD4+ and CD8+ T cells before and after Ipi-Bev treatment. Patient P12 (CR) P8 (PR) P13 (PR) P27 (PR) P37 (SD) PBI-2 (SD) Serum Pre Post Post/Pre CD4+CXCR3+/CD4+ (%) 2.7 63.1 23.2 43.0 39.2 0.9 33.3 43.7 1.3 39.7 42.0 1.1 53.9 52.5 1.0 36.0 43.3 1.2 CD8+CXCR3+/CD8+ (%) 10.1 91.6 9.1 74.2 65.2 71.2 61.1 72.1 71.1 67.2 65.9 97.0 85.6 P10 (PD) P14 (PD) PMGH2 (PD) PBI-7 (PD) PBI-13 (PD) 61.7 53.4 57.9 65.5 41.8 55.2 28.6 35.4 14.3 13.0 60.2 58.8 80.3 75.9 70.1 75.4 84.3 69.0 0.8 30.0 24.8

Wilcoxon rank-sum p-value Supplementary Table S3. Pre-treatment serum levels of cytokines/chemokines were not associated with response (CR/PR vs. SD/PD/Uneval) to Ipi-Bev. Cytokines/ Chemokines BOR Wilcoxon rank-sum p-value SD/PD/Uneval CR/PR N Min Median Max EGF 35 0.3 134.7 509.3 8 23.7 170.0 282.7 0.89 EOTAXIN 3.2 79.3 196.5 49.0 74.0 177.8 0.87 FGF-2 1.2 48.2 131.6 52.5 80.9 0.68 GM-CSF 7.6 26.1 2.2 8.7 28.8 0.36 GRO 551.9 1648.6 231.7 517.6 693.3 0.55 G-CSG 3.1 21.1 114.4 44.0 97.6 0.17 IFNg 0.5 18.0 15.0 0.78 IL-8 18.2 296.5 12.8 110.7 IL-1a 0.4 6.3 307.8 1.9 15.1 0.63 IFNa2 0.8 7.3 94.9 10.9 19.7 0.74 IP-10 11.6 351.8 1563.1 244.3 381.7 2273.2 0.61 MCP-1 411.5 755.9 173.7 340.2 695.8 0.57 MDC 845.4 2171.9 483.1 783.8 1228.9 0.53 MIP-1b 25.5 102.2 2.4 29.6 57.6 0.96 TNFa 0.1 4.0 24.1 3.0 15.3 0.60 VEGF 71.5 331.7 77.1 142.5 0.79

Wilcoxon rank-sum p-value Supplementary Table S4. Pre-treatment serum levels of cytokines/chemokines were not associated with disease control (CR/PR/SD vs. PD/Uneval) in Ipi-Bev-treated patients. Cytokines/ Chemokines DCR Wilcoxon rank-sum p-value PD/Uneval CR/PR/SD N Min Median Max EGF 13 0.3 149.7 506.5 30 23.7 138.7 509.3 0.84 EOTAXIN 45.8 80.2 196.5 3.2 75.7 177.8 0.56 FGF-2 16.8 60.1 127.8 1.2 41.5 131.6 0.28 GM-CSF 4.2 7.6 26.1 7.4 28.8 0.27 GRO 55.1 541.2 1648.6 553.7 1288.3 0.78 G-CSG 8.0 37.0 114.4 3.1 22.1 111.1 0.29 IFNg 0.5 18.0 15.0 0.41 IL-8 1.7 17.4 243.1 18.5 296.5 0.64 IL-1a 13.7 307.8 0.4 4.9 49.2 0.10 IFNa2 4.3 15.5 94.9 0.8 6.3 26.3 0.01 IP-10 120.9 363.1 1552.3 11.6 351.7 2273.2 0.96 MCP-1 168.5 449.0 755.9 359.2 705.7 0.07 MDC 460.5 770.7 1149.3 883.3 2171.9 0.22 MIP-1b 10.7 35.4 86.4 2.4 24.9 102.2 0.16 TNFa 1.4 4.1 14.1 0.1 3.0 24.1 0.35 VEGF 33.8 94.6 211.1 65.0 331.7 0.25

Wilcoxon rank-sum p-value Supplementary Table S5. Fold-changes of serum cytokines/chemokines were not associated with response (CR/PR vs. SD/PD/Uneval) to Ipi-Bev. Cytokines/ Chemokines BOR Wilcoxon rank-sum p-value SD/PD/Uneval CR/PR N Min Median Max EGF 35 0.06 1.06 18.83 8 0.38 1.03 2.37 0.79 EOTAXIN 0.71 1.10 37.85 0.59 1.42 FGF-2 0.49 1.00 50.11 0.28 0.91 2.62 0.27 GM-CSF 0.35 4.15 0.32 0.88 1.95 0.57 GRO 0.56 1.29 194.8 0.73 1.23 2.68 0.55 G-CSG 0.15 8.13 1.04 3.63 0.50 IFNg 0.09 36.98 0.92 41.41 0.84 IL-8 0.04 1.72 19.50 0.14 1.17 15.51 0.61 IL-1a 0.43 1.16 16.14 2.82 14.51 0.18 IFNa2 0.26 1.24 10.11 1.98 10.45 0.69 IP-10 0.42 30.68 1.08 1.74 6.00 0.19 MCP-1 0.95 142.3 0.63 2.56 0.96 MDC 0.33 0.89 142.2 0.62 0.94 1.59 MIP-1b 0.21 1.11 14.70 0.68 1.18 4.04 TNFa 0.36 1.70 14.29 0.87 1.47 6.07 0.86 VEGF 0.07 12.17 0.11 0.82 1.91

Wilcoxon rank-sum p-value Supplementary Table S6. Fold-changes of serum cytokines/chemokines were not associated with disease control (CR/PR/SD vs. PD/Uneval) in Ipi-Bev-treated patients. Cytokines/ Chemokines DCR Wilcoxon rank-sum p-value PD/Uneval CR/PR/SD N Min Median Max EGF 13 0.23 1.00 18.83 30 0.06 1.08 3.50 0.74 EOTAXIN 0.76 1.07 1.34 0.59 1.10 37.85 0.50 FGF-2 0.57 3.11 0.28 50.11 0.55 GM-CSF 1.06 3.05 0.32 0.95 4.15 0.81 GRO 0.78 1.29 6.54 0.56 1.28 194.8 0.99 G-CSG 0.60 6.41 0.15 8.13 0.52 IFNg 4.71 0.09 41.41 0.96 IL-8 0.72 1.72 19.50 0.04 1.51 18.40 0.46 IL-1a 0.43 1.27 7.30 1.21 16.14 0.34 IFNa2 1.17 4.93 0.26 1.35 10.45 0.21 IP-10 0.42 1.20 6.33 0.65 1.59 30.68 0.38 MCP-1 0.62 0.92 1.63 142.3 0.93 MDC 0.45 0.85 0.33 0.94 142.2 0.14 MIP-1b 1.15 2.79 14.70 0.89 TNFa 0.49 1.70 6.62 0.36 1.68 14.29 VEGF 0.27 3.44 0.07 0.64 12.17

Fishers’ exact p-value Response by FLT-31 0.99 Response by fractalkine Supplementary Table S7. Response (CR/PR vs. SD/PD/Uneval) to Ipi-Bev by cytokine expression category. Comparison Fishers’ exact p-value Response by FLT-31 0.99 Response by fractalkine Response by IL-2 Response by IL-3 0.11 Response by IL-4 0.42 Response by IL-5 0.40 Response by IL-6 0.44 Response by IL-7 Response by IL-9 0.69 Response by IL-10 Response by IL-13 Response by IL-15 Response by IL-17 Response by IL-12p40 0.46 Response by IL-12p70 Response by IL-1b 0.70 Response by IL-1ra 0.22 Response by MCP-3 Response by MIP-1a Response by TGFa Response by TNFb Response by SIL-2ra Response by sCD40L 0.31

Supplementary Table S8. Disease control (CR/PR/SD vs Supplementary Table S8. Disease control (CR/PR/SD vs. PD/Uneval) in Ipi-Bev-treated patients by cytokine expression category. Comparison Fishers’ exact p-value Disease-control by FLT-31 0.14 Disease-control by fractalkine 0.49 Disease-control by IL-2 0.16 Disease-control by IL-3 0.99 Disease-control by IL-4 0.32 Disease-control by IL-5 0.73 Disease-control by IL-6 Disease-control by IL-7 Disease-control by IL-9 0.74 Disease-control by IL-10 0.33 Disease-control by IL-13 Disease-control by IL-15 Disease-control by IL-17 0.31 Disease-control by IL-12p40 Disease-control by IL-12p70 Disease-control by IL-1b Disease-control by IL-1ra Disease-control by MCP-3 0.02 Disease-control by MIP-1a Disease-control by TGFa 0.29 Disease-control by TNFb Disease-control by SIL-2ra 0.57 Disease-control by sCD40L

Wilcoxon rank- sum p-values Supplementary Table S9. Pre-treatment cytokine levels according to immune related adverse events (irAEs). N Mean Std Min Median Max Wilcoxon rank- sum p-values IFNa2 Severe irAE 31 14.2 16.6 0.8 11.0 94.9 0.01 No Yes 12 6.2 4.6 3.2 4.8 18.0 IL-1a 23.2 55.0 0.4 7.5 307.8 0.46 13.9 15.8 1.2 4.4 49.2 TNFa 5.6 5.4 4.1 24.1 0.21 3.8 4.0 0.1 15.3 GRO 617.7 360.9 580.9 1648.6 0.17 460.3 208.0 212.7 413.6 963.3 IP-10 515.9 406.1 11.6 373.2 1563.1 0.22 512.3 597.5 120.9 303.2 2273.2 IL-8 41.2 69.5 19.9 296.5 0.30 19.6 29.0 2.5 8.7 105.8

Wilcoxon rank-sum p-values Supplementary Table S10. Relationship between cytokine fold-changes according to irAEs. N Mean Std Min Median Max Wilcoxon rank-sum p-values IFNa2 Severe irAE 31 2.1 2.4 0.3 1.2 10.4 0.51 No Yes 12 1.9 1.1 0.7 1.8 4.0 IL-1a 3.1 4.3 0.4 16.1 0.56 3.0 3.8 0.5 1.4 13.5 TNFa 3.3 14.3 0.43 2.2 0.8 1.3 7.1 GRO 7.8 34.7 0.6 194.8 0.36 2.8 IP-10 5.6 1.5 30.7 0.70 2.3 1.6 6.0 IL-8 4.5 0.0 18.4 0.34 4.7 6.3 19.5

Supplementary Table S11. Clinical responses and survival of patients whose plasma samples were used in antibody response analyses. Patient Clinical Response Survival (months) Alive P6 Partial response 52 Yes P8 51

Cytokines / Chemokines Therapy Fisher’s Exact p-value Supplementary Table S12. Effects of ipilimumab alone and Ipi-Bev on circulating cytokine/chemokine levels. Cytokines / Chemokines Therapy Fisher’s Exact p-value Ipi-Bev Ipi N % IFNa2 25 58.1 14 60.9 0.78 FC <1.5 FC ≥ 1.5 16 37.2 7 30.4 IL-1a 20 46.5 4 17.4 0.36 18 41.9 1 4.3 TNFa 13 56.5 0.31 10 43.5 GRO 26 60.5 69.6 0.59 17 39.5 IP-10 21 48.8 15 65.2 0.3 22 51.2 8 34.8 IL-8 9 39.1 0.61