Taube: Two mechanisms for PD-L1 up-reg in tumors: innate (tumor signaling), and adaptive (IFN-g, reflecting immune reaction) #AACR17
11:11am April 3rd 2017 via Hootsuite
Taube: In mice, PD-L1 expression w/o lymphocytes present. '12 STM ref https://t.co/6x6ZxVJalJ 150 melanocytic lesions: TIL necessary #AACR17
11:09am April 3rd 2017 via Hootsuite
Taube: Shows correlation of pre-Rx tumor PD-L1 expression w/ objective response. Need to look at innate vs adaptive exp of PD-L1 #AACR17
11:08am April 3rd 2017 via Hootsuite
Janis Taube (Hopkins MD) Tumor immunoarchitecture: Add'l predictive factors for cancer immunoRx response #AACR17
11:07am April 3rd 2017 via Hootsuite
Hellman: Opportunities to use targeted or WES as a diagnostic? Need to move beyond TMB as a proxy. #AACR17
11:05am April 3rd 2017 via Hootsuite
Hellman: Need to balance minimal tissue use and information derived is 'usable and generalizable', and reproducible 'abs critical' #AACR17
11:04am April 3rd 2017 via Hootsuite
Hellman: Could be other types of mutations (i.e. CNV reports are starting to appear). No clear reason why mutation matters. #AACR17
11:03am April 3rd 2017 via Hootsuite
Hellman: '16 NEJM https://t.co/Xx9q4M9Grk shows mutations in melanoma #AACR17
Hellman: Mutation burden a 'crude characteristic'. '17 Ref loss of PTEN and I-O resistance https://t.co/EaaxfO6zgQ #AACR17
11:01am April 3rd 2017 via Hootsuite
Hellman: Neoantigen burden 'probably not' a meaningful characteristic; immunol. relevant neoAG appear to be relatively few #AACR17
11:00am April 3rd 2017 via Hootsuite
Hellman: Neoantigen burden <> mutation burden. Can est binding affinity in HLA alleles. Accuracy? '14 ref https://t.co/nYQXfQCYZG #AAC
10:56am April 3rd 2017 via Hootsuite
Hellman: Does mut burden assoc w/PD-L1? Perhaps, but not convincing. Is candidate neoantigen burden meaningful? #AACR17
10:55am April 3rd 2017 via Hootsuite
Hellman: Shows data between high- and low-burden; shares Seiwert ASCO SITC data, Nanostring GEP and mut burden not high corr. #AACR17
10:54am April 3rd 2017 via Hootsuite
Hellman: Yes, WES a reasonable proxy for tumor mutation burden. Points out that WES targeted panels were not designed for purpose #AACR17
10:51am April 3rd 2017 via Hootsuite
Matthew Hellman (Mem Sloan Kettering NY) DNA-based approaches to examining determinant of response and resistance to PD-1 blockade #AACR17
10:50am April 3rd 2017 via Hootsuite
Beechem: Can invert the mask, to select the remainder (tumor microenvironment). Poster 3810/6 #AACR17 with D Rimm (Yale)
10:38am April 3rd 2017 via Hootsuite
Beechem: The mask will then selectively illuminate only the tumor cells, PanCK labeled; masking then all tags are released #AACR17
10:36am April 3rd 2017 via Hootsuite
Beechem: Able to do 'phenotypic reading and writing' - took colorectal ca slice; PanCK imaging. Color image = masked #AACR17
10:35am April 3rd 2017 via Hootsuite
Beechem: Micromirror-controlled cleavage is specific to the spot; shows quantitation of each area, single-molecule counting #AACR17
10:33am April 3rd 2017 via Hootsuite
Beechem: The cleaved tags are then going through the regular analysis - a localized analysis. 4-color microscope #AACR17
Beechem: Based on that region of interest ID'd by microscopy, can ID and select, UV-cleave, aspirate oligos and collect. #AACR17
10:31am April 3rd 2017 via Hootsuite
Beechem: A design for a digital, spatial profiling microscope. Able to label antibodies, illuminate region of interest and cleave #AACR17
10:30am April 3rd 2017 via Hootsuite
Mills: WES 'mutation was there' but not called. Can inform immuno-oncology studies by simultaneous analysis of DNA, RNA, protein #AACR17
10:27am April 3rd 2017 via Hootsuite
Mills: Cross-platform between nCounter SNV vs deep WES; NRAS Q61R missed via WES. T200 platform (targeted) found at 25% AF #AACR17
10:25am April 3rd 2017 via Hootsuite
Mills: Work is in-press (Genome Med, Reuben et al); #AACR17 poster 5563. RNA/Protein analysis; PI3K/AKT activation, ImmunoRx resistant
10:24am April 3rd 2017 via Hootsuite
Mills: FFPE looking at 104 SNVs, 770 RNAs, 29 protein targets. 5ng DNA, 100ng RNA, can work with 1 5um slide #AACR17
10:23am April 3rd 2017 via Hootsuite
Mills: 3D biology utilization - protein vs CNV; protein vs mRNA - plots show where only protein indicated (no CNV, mRNA present) #AACR17
10:22am April 3rd 2017 via Hootsuite
Mills: RP protein array (RPPA) vs nCounter: overall 'high correlation' (found PhophoEGFR Ab x-reacts w/phophoHER2) #AACR17
10:20am April 3rd 2017 via Hootsuite
Mills: Shows technical, biological replicate data: r=0.99, r=0.96. 'Almost unbelievable correlation'. Low counts (5 or 10) reprod #AACR17
10:19am April 3rd 2017 via Hootsuite
Mills: Can easily 30-40 antibodies at a time; using sparse unbiased pathway representation - can impute pathway activity #AACR17
10:18am April 3rd 2017 via Hootsuite
Mills: Their protein work: cleavable linker DNA on Ab - validated via IHC, RP protein array; have immune-oncology platform in-play #AACR17
10:17am April 3rd 2017 via Hootsuite
Mills: Chart of DIN to AF, 97-98% concordance. Input is only 7ng (maximum); can design 'very spec probes' hard NGS var's to detect #AACR17
10:16am April 3rd 2017 via Hootsuite
Mills: cfDNA down to 0.5%; detection rate 97.8% (1 FN, 45/46 samples). NRAS mutation missed - may be technical problem #AACR17
10:14am April 3rd 2017 via Hootsuite
Mills: 25 genes, have known samples w/ultra-deep seq, some work on cfDNA. FFPE has AF's from 2.4% - 50%; DIN from 1.7-6.2 #AACR17
10:13am April 3rd 2017 via Hootsuite
Mills: Used probesets, with perfect / imperfect matches. Can displace with mutant probe. Vantage 3D: picked up DNA SNVs #AACR17
10:12am April 3rd 2017 via Hootsuite
Mills: Did work on RP protein array; not optimal for the clinic. Attracted to NanoString - broadened from protein, to DNA/RNA #AACR17
10:10am April 3rd 2017 via Hootsuite
Gordon Mills (NanoString workshop) Powering precision oncology w/3D biology technology; intro by Joe Beecham #AACR17
10:09am April 3rd 2017 via Hootsuite
Zitvogel: Onto FMT in germ-free mice: more unpublished data (won't post). ('15 Science https://t.co/bGkekHTkzg ) #AACR17
8:58am April 3rd 2017 via Hootsuite
Zitvogel: As part of Meta-HIT, looked at NSCLC and mRCC. Shows unpublished data; groups up- and down-regulated. #AACR17
8:55am April 3rd 2017 via Hootsuite
Zitvogel: '15 Science https://t.co/oXgW52Tegh Commensal Bifidobacterium helping facilitate anti-PD-L1 activity #AACR17
8:52am April 3rd 2017 via Hootsuite
Zitvogel: Could minimalist microbiome normalize the cancer-immune set point? Synergy bet tumor-targeted and immune-targeted methods #AACR17
8:50am April 3rd 2017 via Hootsuite
Zitvogel: Gut immune system controlling inflamm regions at distant site. Exert functions - called dysbiosis. https://t.co/aXerWGDbig #AACR17
8:49am April 3rd 2017 via Hootsuite
Zitvogel: Cancer-immunity cycle '13 Chen figure https://t.co/l5SUhBDh40 Describes 'cold' vs 'hot' tumors https://t.co/5esvSNeD7i #AACR17
8:48am April 3rd 2017 via Hootsuite
Laurence Zitvogel: A new era of immuno-oncology: anticancer probiotics #AACR17
8:45am April 3rd 2017 via Hootsuite
Allison: Can see CTLA-4 depletes Treg; increase CD4 effector; pockets of CD8 increase. Treg freq correlates w/tumor growth #AACR17
8:39am April 3rd 2017 via Hootsuite
Allison: Uses 43-parameter CyTOF (Fluidigm DVS tech), +/- checkpoint blockade, to ID cells impt for anti-tumor effect #AACR17
8:34am April 3rd 2017 via Hootsuite
Allison: What has been lost - how different aCTLA-4 is to aPD1: hard-wired; CD28; priming; clonal diversity; affects CD4 T-cells #AACR17
8:33am April 3rd 2017 via Hootsuite
Allison: Critical issues - det cellular and molecular mechanisms involved in anti-tumor effect; combine best std-of-care w/agents #AACR17
8:32am April 3rd 2017 via Hootsuite
Allison: 60% surv after 2y (ASCO2016); good % may be alive after 10y (given prior K-M data). #AACR17
8:31am April 3rd 2017 via Hootsuite
Allison: Shows results from PD-L1 NEJM '12 https://t.co/ZPeLurKcsY More recent work is combining aCTLA-4 and aPD-1 65% clin activity #AACR17
8:30am April 3rd 2017 via Hootsuite
