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Prof. Kwon's Immune Cell Trafficking and Infiltration, First Steps

Recognising it is not enough
if you never arrive

Most immunology is about recognition. But there is a problem before that โ€” the cell has to get there.
The tumours in this paper have plenty of mutations, intact antigen presentation, and no T cells. The paper writes: anti-PD1 alone recruits lymphocytes but does not drive them into the tumour core.
These twenty lessons teach that grammar and then score that claim against coordinates. With 100,000 cells you measure 'infiltration' five ways โ€” and the five disagree. Choosing a metric turns out to be choosing a conclusion.

๐Ÿงญ chemokines๐Ÿ”— four steps๐Ÿ—บ๏ธ 100k cells ๐Ÿ“ five metrics๐Ÿ Python๐Ÿ”ฌ Xenium๐Ÿ‡ฌ๐Ÿ‡ง English
Start lesson 1 โ†’

How you'll learn

๐ŸงญLearn the grammar first

Chemokines set direction, selectins slow the cell down, and only past the chemokine checkpoint do integrins unfold. Block any one of seven steps and the T cell never arrives.

๐Ÿ“Measure it five ways

Count, fraction, density, distance, neighbourhood composition. Same data, five different answers โ€” the first three favour the combination, the last two favour the control.

๐Ÿ”One number, two stories

In the combination, lymphocytes sit farther from tumour cells. Did they fail to enter โ€” or had they already cleared that area? Proliferating tumour cells fell 4,041 โ†’ 502.

โš–๏ธCall the undecidable undecided

Split the paper's claim into three: two are supported, one is undecidable. The numbers point the other way, but the alternative explanation could not be ruled out.

Full curriculum

01
๋ฉด์—ญ์€ ๋ถ™๋ฐ•์ด๊ฐ€ ์•„๋‹ˆ๋‹ค โ€” ๋ชธ์„ ๋„๋Š” ์„ธํฌ๋“ค
๋…ผ๋ฌธ Fig. 5E ใ€Œdoes not induce their infiltration into the coreใ€
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02
์ผ€๋ชจ์นด์ธ โ€” ๋†๋„ ๊ธฐ์šธ๊ธฐ๊ฐ€ ๋ฐฉํ–ฅ์„ ๋งŒ๋“ ๋‹ค
์ฃผํ™”์„ฑ(chemotaxis) ยท CXCL9/10 ๊ณผ CXCR3
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03
ใ€์‹ค์Šตใ€‘ ์ขŒํ‘œ๊ฐ€ ๋ถ™์€ ์„ธํฌ 10๋งŒ ๊ฐœ๋ฅผ ์—ฐ๋‹ค
GSE285341 Xenium ยท ์กฐ๊ฑด๋งˆ๋‹ค 25,000๊ฐœ
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04
์ ‘์ฐฉ 4๋‹จ๊ณ„ โ€” ๊ตฌ๋ฅด๊ธฐ ยท ํ™œ์„ฑํ™” ยท ๋ถ™๊ธฐ ยท ๋น ์ ธ๋‚˜๊ฐ€๊ธฐ
๋ฐฑํ˜ˆ๊ตฌ ์œ ์ถœ(extravasation)์˜ ๋ฌธ๋ฒ•
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05
์…€๋ ‰ํ‹ด ยท ์ธํ…Œ๊ทธ๋ฆฐ ยท ICAM โ€” ์ด๋ฆ„์ด ๋งŽ์€ ์ด์œ 
์ ‘์ฐฉ ๋ถ„์ž ๊ฐ€์กฑ ์ •๋ฆฌ
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06
๋ฆผํ”„์ ˆ โ€” ๋งŒ๋‚˜๋„๋ก ์„ค๊ณ„๋œ ๊ฑด๋ฌผ
T๊ตฌ์—ญ ยท B์—ฌํฌ ยท ๊ทธ๋ฆฌ๊ณ  CCL19/21
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07
HEV โ€” ํ˜ˆ์•ก์—์„œ ๋ฆผํ”„์ ˆ๋กœ ๋“ค์–ด๊ฐ€๋Š” ์ „์šฉ๋ฌธ
๊ณ ๋‚ดํ”ผ์„ธ์ •๋งฅ(high endothelial venule)
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08
ํ”„๋ผ์ด๋ฐ ๋‹ค์Œ โ€” ๊ท€์†Œ์ˆ˜์šฉ์ฒด๊ฐ€ ๋ชฉ์ ์ง€๋ฅผ ์ •ํ•œ๋‹ค
imprinting ยท ์–ด๋””์„œ ๊นจ์–ด๋‚ฌ๋А๋ƒ๊ฐ€ ์–ด๋””๋กœ ๊ฐˆ์ง€๋ฅผ ์ •ํ•œ๋‹ค
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09
์กฐ์ง ์ƒ์ฃผ โ€” ๋‚˜๊ฐ€์ง€ ์•Š๊ธฐ๋กœ ํ•œ ์„ธํฌ๋“ค
Trm ยท CD69 ์™€ CD103 ยท ๊ทธ๋ฆฌ๊ณ  ์ข…์–‘์—์„œ์˜ ๋œป
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10
์ข…์–‘ ํ˜ˆ๊ด€์€ ์ •์ƒ ํ˜ˆ๊ด€์ด ์•„๋‹ˆ๋‹ค
๋น„์ •์ƒ ํ˜ˆ๊ด€ ยท ๊ทธ๋ฆฌ๊ณ  ํ˜ˆ๊ด€ ์ •์ƒํ™”๋ผ๋Š” ์—ญ์„ค
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11
ใ€์‹ค์Šตใ€‘ ์‚ฌ๋ง‰ ยท ๋ฐฐ์ œ ยท ์—ผ์ฆ โ€” ์„ธ ํ‘œํ˜„ํ˜•์„ ์ขŒํ‘œ๋กœ ๋‹ค์‹œ ๋ณธ๋‹ค
๋…ผ๋ฌธ Fig. 1A ยท Saltz ๋“ฑ์˜ ๋ถ„๋ฅ˜๋ฅผ ๊ณต๊ฐ„์—์„œ
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12
๊ธฐ์งˆ๊ณผ CAF โ€” ๋ฌผ๋ฆฌ์  ์žฅ๋ฒฝ
์ฝœ๋ผ๊ฒ ยท CXCL12 ยท TGF-ฮฒ
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13
์ผ€๋ชจ์นด์ธ์„ ์ง€์šด๋‹ค โ€” CXCL9/10 ์ด ๊บผ์ง€๋Š” ๋ฐฉ๋ฒ•
ํ›„์„ฑ์œ ์ „ํ•™์  ์นจ๋ฌต ยท ๋‹ˆํŠธ๋กœํ™” ยท ๊ทธ๋ฆฌ๊ณ  ์ƒ์œ„ ๊ฒฝ๋กœ
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14
ใ€์‹ค์Šตใ€‘ ๋„ค ์กฐ๊ฑด์—์„œ ์ผ€๋ชจ์นด์ธ ์ถ•์„ ์žฐ๋‹ค
GSE285341 Xenium ยท ๊ทธ๋ฆฌ๊ณ  ๊นŠ์ด๋ผ๋Š” ํ•จ์ •
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15
์นจ์œค์„ ์–ด๋–ป๊ฒŒ ์žฌ๋‚˜ โ€” ๊ฐœ์ˆ˜ ยท ๋ฐ€๋„ ยท ๊ฑฐ๋ฆฌ
๋…ผ๋ฌธ Fig. 4E ยท Fig. 5E ยท ๋ฌด์—‡์„ ์žฌ๋А๋ƒ๋กœ ๊ฒฐ๋ก ์ด ๋ฐ”๋€๋‹ค
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16
ใ€์‹ค์Šตใ€‘ ๊ฒฝ๊ณ„์—์„œ ์ค‘์‹ฌ๊นŒ์ง€ โ€” ๊ฑฐ๋ฆฌ ํ”„๋กœํŒŒ์ผ์„ ๊ทธ๋ฆฐ๋‹ค
์ข…์–‘์„ธํฌ๊นŒ์ง€์˜ ๊ฑฐ๋ฆฌ ยท ์กฐ๊ฑด๋งˆ๋‹ค ์–ด๋–ป๊ฒŒ ๋‹ค๋ฅธ๊ฐ€
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17
ใ€์‹ค์Šตใ€‘ '๊ฐ€์žฅ์ž๋ฆฌ์—๋งŒ ์žˆ๋‹ค' ๋ฅผ ์ˆซ์ž๋กœ ํŒ์ •ํ•œ๋‹ค
์ด์›ƒ ๋ฐ˜์ง€๋ฆ„ 50 ยตm ์•ˆ์˜ ์ข…์–‘์„ธํฌ ๋น„์œจ
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18
TLS โ€” ์ข…์–‘ ์•ˆ์— ๋ฆผํ”„์ ˆ์„ ์ง“๋Š”๋‹ค
3์ฐจ ๋ฆผํ”„๊ตฌ์กฐ ยท ๊ทธ๋ฆฌ๊ณ  ์šฐ๋ฆฌ ์ž๋ฃŒ์˜ ๋ฆผํ”„๊ตฌ ๋ญ‰์นจ
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19
ใ€์‹ค์Šตใ€‘ ๋…ผ๋ฌธ Fig. 5 ์˜ '์ค‘์‹ฌ ์นจํˆฌ' ์ฃผ์žฅ์„ ์ฑ„์ ํ•œ๋‹ค
๋…ผ๋ฌธ Fig. 5BยทE โ€” ์ขŒํ‘œ๋กœ ํŒ์ •ํ•  ์ˆ˜ ์žˆ๋Š”๊ฐ€
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20
์ •๋ฆฌ โ€” ๋“ค์—ฌ๋ณด๋‚ด๋Š” ์ผ์ด ์™œ ์ด๋ ‡๊ฒŒ ์–ด๋ ค์šด๊ฐ€
20๊ฐ• ยท ์ด ๊ฐ•์˜๊ฐ€ ๋‚จ๊ธฐ๋Š” ๋ชฉ๋ก
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