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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

One last point: don't use tobacco.

It causes cancer

doi.org/10.1093/molb...

(also respiratory and pulmonary diseases, cardiovascular and vascular diseases, diabetes mellitus, and reproductive and sexual impairment).

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

Together, these findings support an interpretation that enhanced ICI response in KRAS G12C-mutant tumors arises from tobacco-driven mutagenesis and its immunogenic consequences, rather than from variant-specific oncogenic or immunologic properties.

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

By integrating published clinical outcome data, we have shown that increasing exposure to tobacco predicts lower hazard ratios and higher response rates to immune-checkpoint inhibition.

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

Our analyses point to the importance of mutagenic context: KRAS G12C is enriched for the tobacco-associated SBS4 mutational signature, which is strongly correlated with tumor mutation burden across lung adenocarcinomas.

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

To clarify the effect of tobacco-associated mutagenesis, we used data from Litchfield et al. to model the impact of tobacco-driven tumor mutational burden on immune-checkpoint inhibition. Predicted response rates increase sharply at low–moderate exposure to SBS4 (tobacco).

doi.org/10.1016/j.ce...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

To clarify the effect of tobacco-associated mutagenesis, we used data from Samstein et al. to model the impact of tobacco-driven tumor mutation burden on immune-checkpoint inhibition outcomes. As SBS4 (tobacco exposure) increases, the predicted hazard ratio declines.

www.nature.com/articles/s41...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

Because tobacco smoke exposure contributes to both KRAS G12C mutations and to increased TMB, it follows that KRAS G12C-mutant tumors exhibit significantly increased TMB compared to KRAS G12D tumors.

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

Smoking is a major contributor to increased tumor mutational burden in non-small-cell lung cancer. Tobacco smoke-related SBS4-attributed mutation fraction and TMB were significantly correlated across LUAD tumors.

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

We examined the tobacco mutational signature and KRAS mutation frequency in tumors. KRAS G12C-mutant tumors showed a significantly higher proportion of mutations attributable to the SBS4 tobacco-associated mutational signature compared to KRAS G12D.

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

We analyzed 9,230 lung adenocarcinoma (LUAD) tumors to assess the mutational context and oncogenic potential of KRAS G12A and G12V and G12C and G12D variants. Their cancer effect sizes were similar—large compared to variants at other sites of KRAS.

aacrjournals.org/cancerres/ar...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

It has been unclear whether the better outcomes associated with KRAS G12C reflect

• G12C versus G12D allele-intrinsic biology or

• shared dependence on tobacco-induced mutagenesis and elevated tumor mutation burden (TMB).

authors.elsevier.com/a/1ls3ocYZOi...

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

KRAS G12C mutations in non-small cell lung cancer (NSCLC) have been associated with improved immune-checkpoint inhibition (ICI) outcomes.

doi.org/10.1016/j.lu...

Redirecting

doi.org

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Jeffrey Townsend @jeffreytownsend.bsky.social · 1h

Just out in Lung Cancer:

KRAS G12C-associated immunotherapy benefit in NSCLC
is substantially mediated by tobacco-induced tumor mutation burden—not allele-specific effects.

authors.elsevier.com/a/1ls3ocYZOi...

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Reposted by Jeffrey Townsend

EssJay PURPLE PURPOSE @purplepurpose.bsky.social · 4d

Flu & covid vax day — & I’m still uncertain which mRNA to ask for. Do I wait for Novavax availability? Last year the other place was all atweet with knowledgable opinions; this year I‘m lost.

“One of those” plus the added idiocy of my 4th guess.

Wordle 1,574 5/6*

⬜🟨⬜⬜⬜
🟩⬜⬜🟩🟩
🟩⬜⬜🟩🟩
🟩🟩⬜🟩🟩
🟩🟩🟩🟩🟩

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Reposted by Jeffrey Townsend

Yale Cancer Center @yalecancer.bsky.social · 11d

Some #lungcancers with #KRAS G12C mutations respond to #immunotherapy bc of⬆️ mutation load from #tobacco exposure. Smoking history + overall mutation burden are better guides for treatment than KRAS status alone.
lungcancerjournal.info/article/S016...
@jeffreytownsend.bsky.social

KRAS G12C-associated immunotherapy benefit in NSCLC is substantially mediated by tobacco-induced tumor mutation burden, not allele-specific effects

KRAS G12C mutations in non-small cell lung cancer (NSCLC) have been associated with improved immune-checkpoint inhibition (ICI) outcomes. However, it remains unclear whether this benefit reflects alle...

lungcancerjournal.info

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Reposted by Jeffrey Townsend

Mrs. Betty Bowers @mrsbettybowers.bsky.social · 21d

DISNEY: "OK, we are putting Jimmy Kimmel back on the air. You can resubscribe now."

ME: "I unsubscribed because you immorally bowed to fascism. I'm not going to resubscribe because you immorally bowed to finances."

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Jeffrey Townsend @jeffreytownsend.bsky.social · 21d

Neither Elon Musk Nor Anybody Else Will Ever Colonize Mars - defector.com/neither-elon...

Neither Elon Musk Nor Anybody Else Will Ever Colonize Mars | Defector

Mars does not have a magnetosphere. Any discussion of humans ever settling the red planet can stop right there, but of course it never does. Do you have a low-cost plan for, uh, creating a gigantic ac...

defector.com

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Reposted by Jeffrey Townsend

Lisa Guerrero @lisaguerrero.bsky.social · 22d

Bye bye, rodent nation.
#BoycottDisney

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Reposted by Jeffrey Townsend

Jeffrey Townsend @jeffreytownsend.bsky.social · Aug 19

will be speaking in

The Distinguished Speaker Series: AI & Health Science

📅 September 19, on “Dismantling the Coarse Paradigm of Cancer ‘Drivers’ and ‘Passengers’”

📍 University at Buffalo Clinical and Translational Science Institute

In person or Zoom — register 🔗: qrco.de/AIHS-DSS

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Jeffrey Townsend @jeffreytownsend.bsky.social · 29d

Student performance tracks district income—linear in some states, leveling in others. It’s steepest in less-affluent states, and math slips from grade 3→8. Our kids deserve better than fate by zip code—and the variance in slope tells us we can do better.

🔗 journals.plos.org/plosone/arti...

The functional form of the association between K-12 student performance and household income in U.S. school districts

It is well-known that income can correlate with the academic performance of K-12 students in the United States (U.S.). However, the mathematical relationship between income and K-12 performance, and h...

journals.plos.org

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Reposted by Jeffrey Townsend

Jen Bendery @jbendery.bsky.social · Sep 1

Photo passed along from a federal employee from inside the Dept of Labor building, where a giant Orwellian image of Trump's face is now draped outside.

Big Brother is watching.

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Reposted by Jeffrey Townsend

Alison Feder @alisonfeder.bsky.social · Sep 10

Sam Hart describes and applies a method to distinguish differences in mutational processes between groups of cancers without signature decomposition (joint work with @kelleyharris.bsky.social and in collaboration with @nalcala.bsky.social )! #Genomics 🖥️ 🧬

www.biorxiv.org/content/10.1...

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Reposted by Jeffrey Townsend

Alison Feder @alisonfeder.bsky.social · Sep 10

Elena Romero led a new preprint detailing joint work with Lillian Cohn's lab at Fred Hutch describing really crazy parallelism in in vivo HIV escape from broadly neutralizing antibodies! #VirEvol #evoSky

www.biorxiv.org/content/10.1...

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Reposted by Jeffrey Townsend

Jon Cooper @joncooper-us.bsky.social · Sep 5

California, Oregon and Washington announced yesterday they’ve created their own health alliance, saying the CDC has become “a political tool that increasingly peddles ideology instead of science.”

New York, Massachusetts, Connecticut, Delaware, Pennsylvania and Rhode Island have now done the same.

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Jeffrey Townsend @jeffreytownsend.bsky.social · Sep 6

youtube.com/shorts/AYm9w...

For our scientists

YouTube video by Elle Cordova

youtube.com

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