Cancer Research and Treatment

Original Articles

Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer: Su-Jung Kim, Soyeon Kim, Dong-Wan Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yusoo Lee, Jaemoon Koh, Yoon Kyung Jeon, Dae Seog Heo; Cancer Res Treat. 2019;51(3):1231-1240. Published online December 31, 2018; DOI: https://doi.org/10.4143/crt.2018.486

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Purpose
The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer.
Materials and Methods
We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed.
Results
PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163).
Conclusion
PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.

Citations

Citations to this article as recorded by

Immunomodulatory role of oncogenic alterations in non-small cell lung cancer: a review of implications for immunotherapy
Maritza Ramos-Ramírez, Enrique Caballe-Pérez, José Lucio-Lozada, Eunice Romero-Nuñez, Cesar Castillo-Ruiz, Lorena Dorantes-Sánchez, Diana Flores-Estrada, Gonzalo Recondo, Pedro Barrios-Bernal, Luis Cabrera-Miranda, Heyman Bravo-Dominguez, Norma Hernández-
Cancer and Metastasis Reviews.2025;[Epub] CrossRef
Association of PD-L1 expression and clinical outcomes in ROS1 - rearranged advanced non-small cell lung cancer treated with crizotinib
Huixian Zhang, Ziheng Zhang, Ningning Yan, Xingya Li
Frontiers in Oncology.2024;[Epub] CrossRef
Co-Occurrence of ALK rearrangement and KRAS G12C mutation in NSCLC: Report of two cases
M Siringo, F Larocca, A Spagnuolo, G Gentile, M Anile, D Diso, D Santini, A Gelibter
Current Problems in Cancer: Case Reports.2024; 14: 100291. CrossRef
Characterizing the immune tumor microenvironment in ALK fusion-positive lung cancer: state-of-the-art and therapeutical implications
Marco Sposito, Serena Eccher, Luca Pasqualin, Ilaria Mariangela Scaglione, Alice Avancini, Daniela Tregnago, Ilaria Trestini, Jessica Insolda, Adele Bonato, Stefano Ugel, Lisa Derosa, Michele Milella, Sara Pilotto, Lorenzo Belluomini
Expert Review of Clinical Immunology.2024; 20(8): 959. CrossRef
Comparing Genomic Profiles of ALK Fusion-Positive and ALK Fusion-Negative Nonsmall Cell Lung Cancer Patients
Wenchao Xia, Jing Yang, Hongbin Li, Ling Li, Jinfeng Liu
Global Medical Genetics.2024; 11(2): 175. CrossRef
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Shanshan Chen, Jingyi Tang, Fen Liu, Wei Li, Ting Yan, Dangang Shangguan, Nong Yang, Dehua Liao
Frontiers in Immunology.2023;[Epub] CrossRef
High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis in ALK-Rearranged Non-Small Cell Lung Cancer
Xia Tian, Yalun Li, Qin Huang, Hao Zeng, Qi Wei, Panwen Tian
Biomolecules.2023; 13(6): 991. CrossRef
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Annkristin Heine, Stefanie Andrea Erika Held, Solveig Nora Daecke, Chrystel Flores, Peter Brossart
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Ye Guo, Hanfei Guo, Yongfei Zhang, Jiuwei Cui
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The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase‐positive non‐small cell lung cancer
Ja Yoon Heo, Changhee Park, Bhumsuk Keam, Chan‐Young Ock, Miso Kim, Tae Min Kim, Dong‐Wan Kim, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Dae Seog Heo
Thoracic Cancer.2019; 10(11): 2117. CrossRef

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Impact of Mucin Proportion in the Pretreatment MRI on the Outcomes of Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy: Eunji Kim, Kyubo Kim, Se Hyung Kim, Sae-Won Han, Tae-You Kim, Seung-Yong Jeong, Kyu Joo Park, Jaemoon Koh, Gyeong Hoon Kang, Eui Kyu Chie; Cancer Res Treat. 2019;51(3):1188-1197. Published online December 20, 2018; DOI: https://doi.org/10.4143/crt.2018.434

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer.
Materials and Methods
Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed.
Results
After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance.
Conclusion
Poor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.

Citations

Citations to this article as recorded by

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BMC Gastroenterology.2024;[Epub] CrossRef
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BJS Open.2022;[Epub] CrossRef
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David D. Childs, Caio Max Sao Pedro Rocha Lima, Yi Zhou
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R.J. Goiffon, A. O'Shea, M.G. Harisinghani
Clinical Radiology.2021; 76(12): 879. CrossRef
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Cancers.2020; 13(1): 16. CrossRef

10,211 View
175 Download
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