Speaker
Description
The combination of chemoradiotherapy (CRT) and immune checkpoint inhibition (ICI) in unresectable stage III NSCLC yields markedly divergent outcomes depending on treatment sequencing: consolidation ICI following CRT confers significant survival benefits,¹ whereas concurrent administration fails to improve survival.² This paradox implicates radiation-induced remodeling of the tumor-immune microenvironment as a key, yet poorly understood, determinant of ICI response.
We applied Opal multiplex immunofluorescence (AKOYA Biosciences) to resected NSCLC following neoadjuvant chemotherapy (CHT, n=16), CRT (n=22), or primary resection (n=10), with matched pre-treatment biopsies in a subset. A six-plex panel (CD8, CD4, FOXP3, CD20, CD68, PanCK) was quantified in QuPath to profile the immune composition across tissue compartments and classify the tumor ecosystem by KNN into inflamed, excluded, and cold phenotypes.
Tumors resected after CRT showed selective depletion of CD20+ B cells at the invasive margin compared to CHT and primary resection (p=0.01). FOXP3+ regulatory T cell density also differed significantly across treatment groups (p=0.02), with highest density observed after CHT, while CD8+ effector infiltration was preserved following CRT and CHT. These findings suggest cytotoxic treatment preferentially remodels humoral and immunoregulatory compartments at the tumor-stroma interface, revealing spatial immune barriers relevant to subsequent immunotherapy response.
Bibliography
@article{1,
title = {Five-{Year} {Survival} {Outcomes} {From} the {PACIFIC} {Trial}: {Durvalumab} {After} {Chemoradiotherapy} in {Stage} {III} {Non}–{Small}-{Cell} {Lung} {Cancer}},
volume = {40},
issn = {0732-183X, 1527-7755},
shorttitle = {Five-{Year} {Survival} {Outcomes} {From} the {PACIFIC} {Trial}},
url = {https://ascopubs.org/doi/10.1200/JCO.21.01308},
doi = {10.1200/JCO.21.01308},
language = {en},
number = {12},
urldate = {2026-05-10},
journal = {Journal of Clinical Oncology},
author = {Spigel, David R. and Faivre-Finn, Corinne and Gray, Jhanelle E. and Vicente, David and Planchard, David and Paz-Ares, Luis and Vansteenkiste, Johan F. and Garassino, Marina C. and Hui, Rina and Quantin, Xavier and Rimner, Andreas and Wu, Yi-Long and Özgüroğlu, Mustafa and Lee, Ki H. and Kato, Terufumi and De Wit, Maike and Kurata, Takayasu and Reck, Martin and Cho, Byoung C. and Senan, Suresh and Naidoo, Jarushka and Mann, Helen and Newton, Michael and Thiyagarajah, Piruntha and Antonia, Scott J.},
month = apr,
year = {2022},
pages = {1301--1311},
}
@article{2,
title = {Simultaneous {Durvalumab} and {Platinum}-{Based} {Chemoradiotherapy} in {Unresectable} {Stage} {III} {Non}–{Small} {Cell} {Lung} {Cancer}: {The} {Phase} {III} {PACIFIC}-2 {Study}},
volume = {43},
issn = {0732-183X, 1527-7755},
shorttitle = {Simultaneous {Durvalumab} and {Platinum}-{Based} {Chemoradiotherapy} in {Unresectable} {Stage} {III} {Non}–{Small} {Cell} {Lung} {Cancer}},
url = {https://ascopubs.org/doi/10.1200/JCO-25-00036},
doi = {10.1200/JCO-25-00036},
language = {en},
number = {33},
urldate = {2026-05-10},
journal = {Journal of Clinical Oncology},
author = {Bradley, Jeffrey D. and Sugawara, Shunichi and Lee, Ki Hyeong and Ostoros, Gyula and Demirkazik, Ahmet and Zemanova, Milada and Sriuranpong, Virote and Gelatti, Ana Caroline Zimmer and De Menezes, Juliana Janoski and Zurawski, Bogdan and Newton, Michael and Chander, Pratibha and Jia, Nan and Bielecka, Zofia F. and Özgüroğlu, Mustafa and {on behalf of the PACIFIC-2 Investigators} and Girotto, Gustavo and Peria, Fernanda and Pinto, Gustavo and Marchi, Pedro and Silva, Eduardo and Gelatti, Ana and De Castro, Gilberto and De Azevedo, Sérgio and Faccio, Adilson and Neron, Yeni and Almeida, Thais and De Menezes, Juliana and Zemanova, Milada and Bilek, Ondrej and Roubec, Jaromir and Ostoros, Gyula and Szalai, Zsuzsanna and Laczó, Ibolya and Fülöp, Andrea and Losonczy, György and Gálffy, Gabriella and Goyal, Hari and Asarawala, Nirav and Thungappa, Satheesh and Krishnappa, Rajeev L. and Limaye, Sewanti and Srinivasan, Sankar and Sehran, Mohamed and Mittal, Sushant and Jain, Kartikeya and Bondarde, Shailesh and Okamoto, Isamu and Hayashi, Hidetoshi and Kim, Young Hak and Sakamori, Yuichi and Kubota, Kaoru and Sugawara, Shunichi and Nishio, Makoto and Hida, Toyoaki and Yamaguchi, Teppei and Kondo, Tetsuro and Vazquez Limón, Juan and López-López, Froylan and Alexander, Jorge Alatorre and Alavez, Alejandro Molina and Maciel, Manuel Magallanes and Rangel, Jose Gomez and Leiva, Manuel and Gomez, Henry and Valdiviezo, Natalia and Valdez, Paolo and Bermudez, Vanessa and Figueroa, Alejandro and Tan Chun Bing, Jerry and Dawn Isidro, Marie Grace and Villa, Cherry Pink and Domingo, Barbara and Ortin, Teresa Sy and Cornel, Annielyn Beryl and Parra, Joseph and Dziadziuszko, Rafał and Kowalski, Dariusz and Zurawski, Bogdan and Badzio, Andrzej and Wasilewska-Teśluk, Ewa and Laktionov, Konstantin and Statsenko, Galina and Dvorkin, Mikhail and Levchenko, Evgeniy and Solovyeva, Ekaterina and Vladimirova, Lyubov and Arkhipov, Alexander and Fadeeva, Natalia and Breder, Valery and Kim, Dong-Wan and Kim, Sang-We and Park, Keunchil and Lee, Ki Hyeong and Lee, Sung Sook and Lee, Gyeong-Won and Sriuranpong, Virote and Geater, Sarayut and Chewaskulyong, Busyamas and Chindaprasirt, Jarin and Saichamchan, Siriwimon and Demirkazik, Ahmet and Coskun, Hasan and Goksel, Tuncay and Erman, Mustafa and Özgüroğlu, Mustafa and Kaplan, Muhammed and Phung, Huyen and Nguyen, Khoi and Le, Anh and Nguyen, Dinh Tien},
month = nov,
year = {2025},
pages = {3610--3621},
}
