With @franklowery our new study on attributes of T cells that contribute to successful cell therapy in cancer patients in @ScienceMagazine today w/ colleagues @slgoff_SB, @NCI_CCR_SB @theNCI a TL;DR thread on key findings with caveats :) 1/10

@NCI_CCR_SB has a long history of using tumor infiltrating T cells (TILs) to treat cancers since well.. before I was even born. We analyzed our most successful melanoma ACT trial for cell surface phenotypes in TIL infusion products of patients (aPD1/immunotherapy naive) /2
Surprisingly we found a CD39- TIL subset (CD39-CD69-, DN) associated with ACT-response. TBH we were expecting the opposite (CD39+). We only included CD39 bcz multiple groups (e.g. Simoni et al, 2018) had reported CD39+ as enriching for anti-tumor/neoantigen reactive T cells. /3
CD39- DN TILs RNA/epigenetics resemble stem-like memory progenitors, and in vitro were able to self-renew, and give rise to other CD39+ subsets. OTOH the most dominant subset of patient infusion products were CD39+ CD69+ (DP) and these guys were terminally differentiated.. /4
So, to clarify we specifically analyzed tumor-specific mutation-reactive Tcells. Turns out, ACT-responders had pool of neoantigen-reactive TILs in the CD39- phenotype, while non-responders did not (despite other irrelevant CD39- Tcells) -> not all CD39- T cells are bystanders /5
But previous studies aren’t wrong! Even in responders, we find most neoantigen-reactive TILs are CD39+CD69+ (DP). So, we find the same and agree: CD39 does enrich for mutation reactivity. The nuance is those T cells don’t seem to contribute to response at least in this cohort. /6
In this subgroup, we found no differences btwn resp. vs nonresp. in total # of neoag-specific TILs infused or CD39+ neoag TILs infused. By single cell tracking of mutation-reactive TCRs in patient blood, we found DN TCRs tended to persist longer than DP (they crash faster!). /7
We confirmed this in NYESO-TCR responder by tracking TCR clones over 5yrs! and in Pmel mouse model. In sum: we think stem-like T cells causing ACT response are different from TIL subsets enriched with tumor-reactivity. Recent ICB studies suggest this too (e.g. Kurtulus et al) /8
Caveats: Unsure if neog stem-like Tcells true in other tumor, immuno/cell therapy. We study TIL infusions -> probly diffnt from ex vivo TIL. We can’t comment on PRs/SDs (excluded). In 3 CRs, TIL-infusion was exclusively CD39+DP term diff. Tcells: so.. what’s happening there..? /9
These and many more questions to answer. This is the first in hopefully a series of studies we @NCI_CCR_SB have ongoing with respect to TIL phenotypes, so stay tuned :/ Finally, big thanks to my mentors Steve Rosenberg and Paul Robbins. ~fin

More from Science

1. I find it remarkable that some medics and scientists aren’t raising their voices to make children as safe as possible. The comment about children being less infectious than adults is unsupported by evidence.


2. @c_drosten has talked about this extensively and @dgurdasani1 and @DrZoeHyde have repeatedly pointed out flaws in the studies which have purported to show this. Now for the other assertion: children are very rarely ill with COVID19.

3. Children seem to suffer less with acute illness, but we have no idea of the long-term impact of infection. We do know #LongCovid affects some children. @LongCovidKids now speaks for 1,500 children struggling with a wide range of long-term symptoms.

4. 1,500 children whose parents found a small campaign group. How many more are out there? We don’t know. ONS data suggests there might be many, but the issue hasn’t been studied sufficiently well or long enough for a definitive answer.

5. Some people have talked about #COVID19 being this generation’s Polio. According to US CDC, Polio resulted in inapparent infection in more than 99% of people. Severe disease occurred in a tiny fraction of those infected. Source:
https://t.co/hXlo8qgkD0
Look like that they got a classical case of PCR Cross-Contamination.
They had 2 fabricated samples (SRX9714436 and SRX9714921) on the same PCR run. Alongside with Lung07. They did not perform metagenomic sequencing on the “feces” and they did not get


A positive oral or anal swab from anywhere in their sampling. Feces came from anus and if these were positive the anal swabs must also be positive. Clearly it got there after the NA have been extracted and were from the very low-level degraded RNA which were mutagenized from

The Taq.
https://t.co/yKXCgiT29w to see SRX9714921 and SRX9714436.
Human+Mouse in the positive SRA, human in both of them. Seeing human+mouse in identical proportions across 3 different sequencers (PRJNA573298, A22, SEX9714436) are pretty straight indication that the originals

Were already contaminated with Human and mouse from the very beginning, and that this contamination is due to dishonesty in the sample handling process which prescribe a spiking of samples in ACE2-HEK293T/A549, VERO E6 and Human lung xenograft mouse.

The “lineages” they claimed to have found aren’t mutational lineages at all—all the mutations they see on these sequences were unique to that specific sequence, and are the result of RNA degradation and from the Taq polymerase errors accumulated from the nested PCR process
"The new answer to a 77-year-old problem"

😭


https://t.co/hm9NoaU4nr


https://t.co/8fKDiKjSWc


https://t.co/jkaicC1F2x


https://t.co/PpxWT4Jef4
1/ Automobiles and Intake Fraction. Since cars are back in the news I thought I would retweet this model result I offered in early April 2020. I focused only on 1 micron particles & accounted for windows completely closed & cracked slightly open.


2/ Related air exchange rates were based on experimental results in literature for mid-sized sedans. Particle deposition to indoor surfaces were accounted for, as the surface to volume ratio in a 3 m3 cab is large. An important outcome was the intake fraction (IF)

3/ Here, IF is the number of particles (or virions in collective particles) inhaled by a receptor DIVIDED BY the number or particles (or virions in collective particles) emitted by an infector.

4/ Integrated over the two hour drive (in this example) the IF for all windows closed & a receptor at rest is 0.08 (8% of what comes out of the infectors respiratory system ends up in the respiratory system of the receptor). 8%! That is a very high intake factor.

5/ With additional ventilation from cracking a window open drops the IF to 0.012 (1.2%) still relatively high. Can get lower by opening more windows.

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I hate when I learn something new (to me) & stunning about the Jeff Epstein network (h/t MoodyKnowsNada.)

Where to begin?

So our new Secretary of State Anthony Blinken's stepfather, Samuel Pisar, was "longtime lawyer and confidant of...Robert Maxwell," Ghislaine Maxwell's Dad.


"Pisar was one of the last people to speak to Maxwell, by phone, probably an hour before the chairman of Mirror Group Newspapers fell off his luxury yacht the Lady Ghislaine on 5 November, 1991."
https://t.co/DAEgchNyTP


OK, so that's just a coincidence. Moving on, Anthony Blinken "attended the prestigious Dalton School in New York City"...wait, what? https://t.co/DnE6AvHmJg

Dalton School...Dalton School...rings a

Oh that's right.

The dad of the U.S. Attorney General under both George W. Bush & Donald Trump, William Barr, was headmaster of the Dalton School.

Donald Barr was also quite a


I'm not going to even mention that Blinken's stepdad Sam Pisar's name was in Epstein's "black book."

Lots of names in that book. I mean, for example, Cuomo, Trump, Clinton, Prince Andrew, Bill Cosby, Woody Allen - all in that book, and their reputations are spotless.
1/ Here’s a list of conversational frameworks I’ve picked up that have been helpful.

Please add your own.

2/ The Magic Question: "What would need to be true for you


3/ On evaluating where someone’s head is at regarding a topic they are being wishy-washy about or delaying.

“Gun to the head—what would you decide now?”

“Fast forward 6 months after your sabbatical--how would you decide: what criteria is most important to you?”

4/ Other Q’s re: decisions:

“Putting aside a list of pros/cons, what’s the *one* reason you’re doing this?” “Why is that the most important reason?”

“What’s end-game here?”

“What does success look like in a world where you pick that path?”

5/ When listening, after empathizing, and wanting to help them make their own decisions without imposing your world view:

“What would the best version of yourself do”?