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/ 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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This media manipulation effort was inspired by the success of the "kids in cages" freakout, a 100% Stalinist propaganda drive that required people to forget about Obama putting migrant children in cells. It worked, so now they want pics of Trump "gassing children on the border."

There's a heavy air of Pallywood around the whole thing as well. If the Palestinians can stage huge theatrical performances of victimhood with the willing cooperation of Western media, why shouldn't the migrant caravan organizers expect the same?

It's business as usual for Anarchy, Inc. - the worldwide shredding of national sovereignty to increase the power of transnational organizations and left-wing ideology. Many in the media are true believers. Others just cannot resist the narrative of "change" and "social justice."

The product sold by Anarchy, Inc. is victimhood. It always boils down to the same formula: once the existing order can be painted as oppressors and children as their victims, chaos wins and order loses. Look at the lefties shrieking in unison about "Trump gassing children" today.