Thread by @CharlesMilrod

Picture this:

A patient presents with an enlarging neck mass, and you find this 👇 on your evaluation.

What’s going on? 🤔

A #tweetorial 🧵 1/8

To guide our thoughts, let’s start with two Hodgkin lymphoma (HL) facts-

1) Cancer cells can ⬆️ PD-L1, which interacts with T-cells’ PD-1 and ⬇️ immune activity

2) 🔑 Immune checkpoint inhibitors (ICIs) block the PD-1/PD-L1 interaction & have strong activity in HL 👇

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Why do immune checkpoint inhibitors have such strong activity in HL? 🤔

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The answer is both!

Chromosome 9p24 gains are common in HL and ⬆️ PD-L1/2 levels

🔑 Higher PD-L1 levels are associated with better response

Check out this connection below 👇

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T-regulatory cells are immunosuppressive!

🔑 Compared to reactive lymph nodes, HL has ⬆️ T-regulatory cells and markers of exhaustion👇

… but why would T-cell exhaustion be a *positive* predictor of response? 🤔

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In head & neck cancer, those who respond to ICIs tend to have *higher* levels of exhausted T- cells 👇

🔑 ICIs may have a “cytotoxic revival” effect on exhausted T-cell populations

Possible mechanisms include ICIs 👉 ⬆️ cytotoxic genes and ⬇️ of exhaustive genes

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Future of ICIs? 🤔

In the frontline for advanced HL, SWOG 1826 is evaluating Nivo-AVD vs BV-AVD.

Looking forward to this plenary session at #ASCO23! ⭐️

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Key takeaways:

🔑 Immune checkpoint inhibitors (ICIs) have strong activity in HL

🔑 9p24 amplification 👉 ⬆️ PD-L1

🔑 ICIs may have a “cytotoxic revival” on exhausted T-cells

… and food for thought:

🤔 Will SWOG1826 bring nivolumab to the front-line setting?

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Thanks for sticking around- I hope you learned something new!

Thank you to @lymphomatic for the review 👏

I’d love to hear what the experts would add! @matthew_mei @graham74GC @DavidSteensma @myelomatic @Rcl14L @OllilaTom

For a deeper dive, citations are embedded in the pictures.

Pictures can be found here:

pubmed.ncbi.nlm.nih.gov/10594291/
pubmed.ncbi.nlm.nih.gov/10425256/