T cell-mediated curation and restructuring of tumor tissue coordinates an effective immune response
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Antigen-specific T cells traffic to, are influenced by, and create unique cellular microenvironments. Here we characterize these microenvironments over time with multiplexed imaging in a melanoma model of adoptive T cell therapy and human patients with melanoma treated with checkpoint inhibitor therapy. Multicellular neighborhood analysis reveals dynamic immune cell infiltration and inflamed tumor cell neighborhoods associated with CD8+ T cells. T cell-focused analysis indicates T cells are found along a continuum of neighborhoods that reflect the progressive steps coordinating the anti-tumor immune response. More effective anti-tumor immune responses are characterized by inflamed tumor-T cell neighborhoods, flanked by dense immune infiltration neighborhoods. Conversely, ineffective T cell therapies express anti-inflammatory cytokines, resulting in regulatory neighborhoods, spatially disrupting productive T cell-immune and -tumor interactions. Our study provides in situ mechanistic insights into temporal tumor microenvironment changes, cell interactions critical for response, and spatial correlates of immunotherapy outcomes, informing cellular therapy evaluation and engineering.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
|---|---|
| Enthalten in: |
Cell reports - 42(2023), 12 vom: 26. Dez., Seite 113494 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hickey, John W [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 27.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.celrep.2023.113494 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365763993 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365763993 | ||
| 003 | DE-627 | ||
| 005 | 20240427232020.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.celrep.2023.113494 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1390.xml |
| 035 | |a (DE-627)NLM365763993 | ||
| 035 | |a (NLM)38085642 | ||
| 035 | |a (PII)S2211-1247(23)01506-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hickey, John W |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a T cell-mediated curation and restructuring of tumor tissue coordinates an effective immune response |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.01.2024 | ||
| 500 | |a Date Revised 27.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Antigen-specific T cells traffic to, are influenced by, and create unique cellular microenvironments. Here we characterize these microenvironments over time with multiplexed imaging in a melanoma model of adoptive T cell therapy and human patients with melanoma treated with checkpoint inhibitor therapy. Multicellular neighborhood analysis reveals dynamic immune cell infiltration and inflamed tumor cell neighborhoods associated with CD8+ T cells. T cell-focused analysis indicates T cells are found along a continuum of neighborhoods that reflect the progressive steps coordinating the anti-tumor immune response. More effective anti-tumor immune responses are characterized by inflamed tumor-T cell neighborhoods, flanked by dense immune infiltration neighborhoods. Conversely, ineffective T cell therapies express anti-inflammatory cytokines, resulting in regulatory neighborhoods, spatially disrupting productive T cell-immune and -tumor interactions. Our study provides in situ mechanistic insights into temporal tumor microenvironment changes, cell interactions critical for response, and spatial correlates of immunotherapy outcomes, informing cellular therapy evaluation and engineering | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CODEX | |
| 650 | 4 | |a CP: Cancer | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a Multiplexed tissue imaging | |
| 650 | 4 | |a T cell phenotype | |
| 650 | 4 | |a T cell therapy | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a cancer immunotherapy | |
| 650 | 4 | |a checkpoint inhibitor therapy | |
| 650 | 4 | |a melanoma | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a spatial biology | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 700 | 1 | |a Haist, Maximillian |e verfasserin |4 aut | |
| 700 | 1 | |a Horowitz, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Caraccio, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Yuqi |e verfasserin |4 aut | |
| 700 | 1 | |a Rech, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a Baertsch, Marc-Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Rovira-Clavé, Xavier |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Bokai |e verfasserin |4 aut | |
| 700 | 1 | |a Vazquez, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Barlow, Graham |e verfasserin |4 aut | |
| 700 | 1 | |a Agmon, Eran |e verfasserin |4 aut | |
| 700 | 1 | |a Goltsev, Yury |e verfasserin |4 aut | |
| 700 | 1 | |a Sunwoo, John B |e verfasserin |4 aut | |
| 700 | 1 | |a Covert, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Nolan, Garry P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell reports |d 2012 |g 42(2023), 12 vom: 26. Dez., Seite 113494 |w (DE-627)NLM217067492 |x 2211-1247 |7 nnns |
| 773 | 1 | 8 | |g volume:42 |g year:2023 |g number:12 |g day:26 |g month:12 |g pages:113494 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.celrep.2023.113494 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 42 |j 2023 |e 12 |b 26 |c 12 |h 113494 | ||