Discover and read the best of Twitter Threads about #Immunotherapy

Most recents (24)

Today, in @Nature, we reveal PART 2 of our investigations on

“What IS going on in long-term survivors of #PancreaticCancer (#PDAC)?”

“Is it REALLY the immune system?”

Well…more evidence here - > nature.com/articles/s4158…

Thread below [1/30]
In 2017, we reported in @Nature here -> nature.com/articles/natur… -> that primary tumors of long-term survivors of #PDAC had ~12x more activated CD8 T cells vs. short-term survivors. Now, others had reported this before - but we wanted to know:

“What are the antigens?” Image
Here, the prevailing belief was:

#PDAC has few mutations -> even fewer mutation-derived neoantigens -> neoantigens are unlikely T cell antigens in #PDAC.

But we thought: despite #PDAC’s few mutations, mutation-derived neoantigens may still be T cell antigens in #PDAC survivors
Read 31 tweets
Excited to share that our @NatureBiotech paper with Aviv Regev on Multicellular Programs (MCPs) is now out with a fully automated data-driven method to identify MCPs from #singlecell or spatial data #behindthepaper: go.nature.com/3iQ8fgW nature.com/articles/s4158… (1/19)
Gene programs are often studied within a cell, with each cell considered an “independent entity”. However, cells from the same niche/tissue/organism are not independent, but share external signals, genetic background/lineage, and can directly impact one another. (2/19)
Here we define “Multicellular Programs (MCPs)” as different sets of genes working in concert across different cell types. (3/19)
Read 19 tweets
Do Bone Marrow Haematopoietic Stem and Progenitor Cells (#stemcells) influence #fattyliver, Core Liver Networks, and liver cancer?

Very happy to share our findings in this (5 min read) Tweetorial🧵
More details on bioRxiv:


#livertwitter Schematic depicts a plausible and novel mechanism linking fa
2. In our previous publication in @CellSystemsCP, we used network analysis (#WGCNA) to identify the preserved liver networks (Core-Modules) between species and screened for their genetic regulators (module-eQTLs).
Infographic by Misaki Ouchida:
misakiouchida.com
3. Here you can find a concise review/commentary on our previous paper on core liver networks in @CellRepMed
sciencedirect.com/science/articl…
Read 22 tweets
Really chuffed to share our latest work from Sanjana Lab out in @nature today (nature.com/articles/s4158…).

We tested >12,000 genes to find positive regulators of T cell proliferation to be used for next-gen #immunotherapies.

A thread...
(2/28) T cell therapies have shown the potential to cure patients from #cancer – but even in B cell cancers, relapses outnumber cures… One of the problems is limited T cell persistence. #celltherapy #CARTcell
(3/28) We wanted to find new genes (including genes never expressed in T cells) that could improve T cell persistence. Now, the question was: should we use #crispr activation or directly deliver target genes on a #lentivirus?
Read 30 tweets
Thank you to our Keynote Speakers from COAST-to-COAST for their insightful presentations & to the 8,752 participants who attended @MedNewsWeek Conference in February 2022. It was a pleasure learning from everyone.
I would also like to thank our great team that helped to make this event possible.
@etahmed @CParkMD @drysilay @LVento @lexyv717 @MedNewsWeek @evolusean_
Read 6 tweets
Delighted to share our paper, biorxiv.org/content/10.110… . Huge thanks to @CoukosGeorge for the opportunity as well as all our collaborators, @carmonation. A summary of our main findings:
Orthogonal combinatorial T-cell engineering overcomes homeostatic barriers to engraftment, reprograms TILs as well as the tumor microenvironment and mediates solid tumor regression in the absence of preconditioning or systemic cytokine support @CoukosGeorge, @carmonation
As a proof of principle of orthogonal T-cell engineering, here we successfully combined two main secreted components: an IL-2 variant binding to b/g but not IL-2Ra (promote T-cell stemness), together with the pro-inflammatory alarmin IL-33.
Read 13 tweets
Very happy to present our #proteomics analysis of #lungcancer published today @NatureCancer!🙂
Here’s a walk-through: #MassSpec analysis covering almost 14k proteins in 141 NSCLC tumors revealed 6 proteome subtypes with distinct biology. 1/6
rdcu.be/cBOtU
#NSCLC proteome subtypes are driven by histology, growth pattern, immune cell infiltration, driver mutations, oncogenic pathways, and cell types, suggesting potential clinical value for treatment stratification and #PrecisionMedicine. 2/6
Unexpectedly, #proteogenomics analysis revealed that high neoantigen burden was linked to global hypomethylation, and that complex neoantigens mapping to genomic regions normally not active in lung were produced in immune-cold subtypes. 3/6
Read 6 tweets
Starting #UnsungHeroesImmuno. Did you know about Onesimus and his knowledge of variolation? 1/
#UnsungHeroesImmuno What about Dr. William Augustus Hinton and his work with syphilis? 2/
#UnsungHeroesImmuno We also have Drs. Louis Tompkins Wright and Jane Cook Wright, a father-daughter pair that changed the field of oncology. 3/
Read 14 tweets
1/ Excited to share how T cell therapies kill #leukemia!! multi-omics + new #computational #singlecell tools for longitudinal analysis 👉unexpected answer! cell.com/cell-reports/f…

*👏* @elhamazizi! 🙏 @dpeer Cathy Wu @MDAndersonNews @CPRITTexas @ColumbiaBME @sloan_kettering
2/ We studied donor lymphocyte infusion (DLI) - an #Immunotherapy for relapsed #leukemia after #BMT & the #og of #celltherapy. Previously, we showed DLI reversed T cell exhaustion - but didn't know why/how/which T cells were responsible...
ashpublications.org/blood/article/…
3/ To address these ?'s, we modeled intraleukemic T cell dynamics by integrating longitudinal, multimodal data from ~100K T cells (!) during response (R) or resistance (NR: nonresponder) to DLI.
Read 18 tweets
*NEW ARTICLE*
What does a nephrologist need to know about immune checkpoint inhibitor-associated AKI (ICPi-AKI)?@DavidLeaf9 #Thread
my first #tweetorial with help from @kdjhaveri
jitc.bmj.com/content/9/10/e… (1/11)
Why does it matter? ICPi-AKI can lead to:
*Discontinuation of ICPi therapy
*Irreversible loss of kidney function
*Prolonged courses of immunosuppression (2/11)
We conducted a multicenter study of 429 patients with ICPi-AKI from 30 sites across 10 countries, along with 429 control patients who received ICPis contemporaneously but did not develop ICPi-AKI. This is the largest study to date on ICPi-AKI (3/11)
Read 11 tweets
1)Tweetorial: Immune check point inhibitor related electrolyte disorders short letter @Kidney_Int kidney-international.org/article/S0085-… @renalmyeloma and Vipul Sakhiya - the FDA adverse reporting system.
2) Electrolytes were first mentioned @MayoClinicNeph as most common being hypocalcemia pubmed.ncbi.nlm.nih.gov/29762725/
3)Hyponatremia and other disorders were summarized in a single center study @BWHKidney @BetterCallSeeth @MegSise pubmed.ncbi.nlm.nih.gov/33374011/
Read 10 tweets
#TumorBoardTuesday
💥Wow - this week was TOO much‼️

A🗣️on TMB-high #PancreaticCancer & #Immunotherapy by @DrBonillaOnc

AND our 1st pt-directed🗣️led by @HPolymenis and @StephenVLiu

👉Don’t forget your🆓#CME credit-answer 3 quick❓
Here's the postest🔗
surveymonkey.com/r/6JVHCSG Image
#TumorBoardTuesday
Thursday Case🎀
(Case from 06/01 and 06/02/21)

We discussed #PancreaticCancer and:
✅Cynicism/Nihilism
✅The importance of multi-D care
✅1st line Tx
✅🧬Testing
#Immunotherapy

We captured as much as we could in this moment:
twitter.com/i/events/13999…
#TumorBoardTuesday
Thursday Case🎀
(Case from 06/01 and 06/02/21)

And also this moment:
twitter.com/i/events/14005…
Read 20 tweets
Didnt get chance to answer a great Q on @sarahjulianotts show on @BBCNottingham about having #COVID19 #vaccine the starting #immunotherapy. If the therapy is designed to dampen down your immunity, then it might reduce the overall level of immunity that the vaccine produces.
But in this case, the therapy will start 14 days after vaccine, by which time immunity has often peaked (with Pfizer, maybe slight increase with AZ after this time). Therefore, the therapy will have very little, if any, impact.
And if you are currently on immunotherapy, then the vaccine committee have not precluded you from having the vaccine. Even if the overall response is reduced, I think in most people it will still offer some protection. Worried or unsure - ask your clinical orvaccination team👍
Read 5 tweets
@curecc #ccfac2021 @noza512 @HopkinsMedicine presents on excitement about potential for peptide-based #vaccines as #immunotherapy for #cholangiocarcinoma ! Afterall, tumor recognition is king! And neoantigens critical... ImageImage
@curecc #ccfac2021 @noza512 Combo approach of #neoantigen vaccine + #immunotherapy can be highly effective! But #cholangiocarcinoma has lower #neoantigen burden c/w other tumor, higher T cell exhaustion ImageImage
@curecc #ccfac2021 @noza512 Trial soon to open...hope for opening for #cholangiocarcinoma in near future? Stay tuned! Image
Read 4 tweets
I am thrilled to share our new paper out in @ScienceMagazine! We show that transient disruption of CAR signaling, or "rest", can reinvigorate exhausted CAR-T cells and boost anti-tumor functionality #CART #immunotherapy #IO

Thread 1/

doi.org/10.1126/scienc…
This project began with a simple question: if persistent CAR signaling alone can promote exhaustion, what happens if you turn the CAR off? To test this, we first teamed up with Tom Wandless to create a drug-regulatable CAR system (DD-CAR) that enabled tunable CAR expression
2/
Using a DD-CAR targeting GD2, which exhibits antigen-independent tonic CAR signaling, we observed that "hiding" the CAR during ex vivo expansion dramatically improved CAR-T cell activity, underscoring the importance of preventing tonic CAR signaling to preserve function
3/
Read 15 tweets
I am excited to share our manuscript "Therapeutic Implications of Detecting MAPK-Activating Alterations in Cutaneous and Unknown Primary #Melanomas" published at @CCR_AACR. I think it offers important clinical and translational insights into melanoma. 1/x

clincancerres.aacrjournals.org/content/early/…
All of the genomic and clinical data are available on @cbioportal at cbioportal.org/study/summary?… – thank you to @nikolausschultz Lab, esp @chatila_w + @fjsanchezrivera (bioinformatics/data viz), Arshi Arora (stats), and @sloan_kettering molecular path (all the sequencing) 2/x
This will be a loooong thread for my fellow #melanoma geeks! All other melanoma-curious oncologists and #medtwitter can skip towards the end where I try to highlight some themes for investigating other tumors. 3/x
Read 33 tweets
It is with a heavy heart that we received the very sad news of the passing of our 1st CART19 #Tcell patient. Bill Ludwig was a true #cancer #immunotherapy pioneer and a humble #hero 1/x Image
One of his requests at infusion in 2010 was for cell manufacturing & clinical staff to take a picture with him, so he could have the picture signed. 2/x
This memento he presented to New York Times reporter Denise Grady when she interviewed him in Sept, 2011 for this story 3/x nytimes.com/2011/09/13/hea…
Read 6 tweets
(1/n) A brief #tweetorial highlighting the key aspects of our recent paper in #Cancer Discovery ⁦@CD_AACR⁩ on how cancers with #Chromosomal_Instability evade immune surveillance prompting #metastasis #ScienceTwitter cancerdiscovery.aacrjournals.org/content/early/…
We’ve previously shown that CIN can drive #metastasis through the generation of chronic #inflammation arising from persistent activation of #cGAS #STING signaling. However it wasn’t clear how cells eschewed the immune stimulating effect of this pathway. nature.com/articles/natur…
To address this, we compared isogenic cells with high vs. low levels of CIN and found that cells with high levels of CIN upregulated #ENPP1 an extracellular enzyme shown by @lingyinli1 and Tim Mitchison to hydrolyze #cGAMP
Read 16 tweets
Besides #immunotherapy, how can #CRISPR be used to treat cancer?

Researchers at @CNIOStopCancer just published an exciting proof-of-concept showing how CRISPR can delete cancer-causing gene fusions, selectively killing cancer cells.

I'll elaborate.

nature.com/articles/s4146…
First, let's discuss what gene fusions are. As shown below, fusions result when two genes crash into each other and fuse together.

The resulting protein product is a hybrid. It has some features of Protein A and some of Protein B.

This usually is very bad.
We know that cancer-causing (#oncogenic) fusions have been found in nearly all cancer types. They're more common in pediatric cancers, but still are present in as many as 15-20% of adult cancers.

If present, fusions often are the main drivers of tumor growth.
Read 12 tweets
🎉CELEBRATION ALERT!! We reached 10K followers @NatureCancer - massive thank you to our wonderful community for the warm welcome! Given it is also 10 months of our online life, here are some of our best articles (although all are *fantastic*) #thread 1/n

#10atNatureCancer
January @NatureCancer: Nabel &co @SanofiUS develp #trispecific antibodies against CD3, CD28 and CD38, with preclinical efficacy and safety in humanized mice and NHPs 2/n

go.nature.com/30GlQyH
rdcu.be/b78Zr

#10atNatureCancer
February @NatureCancer: Golub and Co @broadinstitute develop PRISM, a tool for non-oncology drug repurposing in #cancer 3/n

go.nature.com/36zCxQh
rdcu.be/b78ZE

#10atNatureCancer
Read 12 tweets
A Thread on Ancient Indian #Knowledge System and its #KnowledgeAppropriation by outsiders, without crediting the original creator / culture / country. #Plagiarism

#IPR #IntellectualProperty
Reclaim #IntellectualPropertyRights for Bharat that is India.
2020: Study finds 24-hour fasting regenerates stem cells and doubles metabolism:

#Hindus: Practice Ekadashi Vrat (Fasting) which Sanatani Dharmic people are practicing from thousands of yrs for #ImmunoTherapy #IPR

Image
#1 Ancient Yoga Sutras of Patanjali

#2 Remove Mantra, Rituals & Worship to SICKualarize Yoga.

#3 Market it as Christian Yoga.

#KnowledgeAppropriation #IPR Image
Read 3 tweets
@myESMO #ESMO20 as a #trainee can be #overwhelming! So many good studies, some more #practicechanging then others, if you missed some and want to understand (albeit at a simplistic #trainee level), sit back, relax and enjoy as we go through some great data #ESMO20 @OncoAlert
1. #NSCLC: 2 major studies #ADAURA #CROWN for adjuvant #EGFRmNSCLC, and advanced #ALK+ experts can provide better perspective @JackWestMD @n8pennell @StephenVLiu @AMansfieldMD @CharuAggarwalMD @NarjustDumaMD @GlopesMd @DevikaDasMD @OncoAlert
1. A) #ADAURA: Stage IB-IIIA #resected #NSCLC with #EGFRm treated with #Osimertinib vs #placebo [SOC prior to this was adjuvant chemotherapy [cisplatin-based doublet based on #LACE metanalysis- pubmed.ncbi.nlm.nih.gov/18506026/] showed improvement in #DFS @NEJM nejm.org/doi/full/10.10…
Read 19 tweets

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