Cancer Research and Treatment

Original Articles

Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique: Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom; Received November 25, 2024 Accepted February 25, 2025 Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.1128 [Accepted]

Abstract PDF: Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

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Lung and Thoracic cancer

Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis: Soo Han Kim, Hyun Sung Chung, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Insu Kim, Jung Seop Eom; Cancer Res Treat. 2024;56(2):464-483. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.749

Abstract PDF Supplementary Material PubReader ePub: Purpose
Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines.
Materials and Methods
We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total lesion number. Subgroup analysis was performed to identify related factors.
Results
Forty-one studies with a total of 13,133 PLLs were included. The pooled diagnostic yield of RP-EBUS was 0.72 (95% confidence interval [CI], 0.70 to 0.75). Significant heterogeneity was observed among studies (χ²=292.38, p < 0.01, I²=86.4%). In a subgroup analysis, there was a significant difference in diagnostic yield based on RP-EBUS findings (within, adjacent to, invisible), with a risk ratio of 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to, 4.20 (95% CI, 1.89 to 9.32) between within and invisible, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible. There was a significant difference in diagnostic yield based on lesion size, histologic diagnosis, computed tomography (CT) bronchus sign, lesion character, and location from the hilum. The overall complication rate of TBB with RP-EBUS was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%).
Conclusion
Our study showed that TBB with RP-EBUS is an accurate diagnostic tool for PLLs with good safety profiles, especially for PLLs with within orientation on RP-EBUS or positive CT bronchus sign.

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Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study: Taeyun Kim, Tae Won Jang, Chang Min Choi, Mi-Hyun Kim, Sung Yong Lee, Yoon Soo Chang, Kye Young Lee, Seung Joon Kim, Sei Hoon Yang, Jeong Seon Ryu, Jeong Eun Lee, Shin Yup Lee, Chan Kwon Park, Sang Hoon Lee, Seung Hun Jang, Seong Hoon Yoon, Hyung-Joo Oh; Cancer Res Treat. 2023;55(4):1152-1170. Published online May 19, 2023; DOI: https://doi.org/10.4143/crt.2023.493

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group).
Materials and Methods
In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes.
Results
The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5).
Conclusion
This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Citations

Citations to this article as recorded by

KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer
Jae-Sun Choi, Hye-Min Kang, Kiyong Na, Jiwon Kim, Tae-Woo Kim, Junyang Jung, Heejin Lim, Hyewon Seo, Seung Hyeun Lee
Tuberculosis and Respiratory Diseases.2025; 88(1): 138. CrossRef
A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam
Cam Phuong Pham, Thi Thai Hoa Nguyen, Anh Tu Do, Tuan Khoi Nguyen, Thi Anh Thu Hoang, Tuan Anh Le, Dinh Thy Hao Vuong, Dac Nhan Tam Nguyen, Van Khiem Dang, Thi Oanh Nguyen, Van Luan Pham, Minh Hai Nguyen, Thi Huyen Trang Vo, Hung Kien Do, Ha Thanh Vu, Thi
BMC Cancer.2024;[Epub] CrossRef
Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
Cancer Medicine.2024;[Epub] CrossRef
Serum Concentrations of IGF-1R, ERK2, and EGFR and Their Clinical Significance in Patients with Neuroendocrine Tumors
Roksana Duszkiewicz, Janusz Strzelczyk, Elżbieta Chełmecka, Joanna Katarzyna Strzelczyk
Applied Sciences.2024; 14(16): 6998. CrossRef
Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs
Hsu-Yuan Chen, Chia-Hung Chen, Wei-Chih Liao, Yu-Chao Lin, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng, Chih-Yen Tu
BMC Pulmonary Medicine.2024;[Epub] CrossRef
Osimertinib as Second- and ≥Third-Line Treatment in Advanced and Recurrence EGFR-Mutant NSCLC Patients Harboring Acquired T790M Mutation
Mu-Han Peng, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Gee-Chen Chang, Tsung-Ying Yang
Cancers.2024; 16(24): 4174. CrossRef
Effectiveness of first-line anticancer treatment may predict treatment response in further lines in stage III/IV patients with non-small cell lung cancer
Monika Bratova, Jana Skrickova, Magda Matusikova, Karolina Hrabcova, Libor Havel, Leona Koubkova, Michal Hrnciarik, Jana Krejci, Ondrej Fischer, Martin Svaton, Kristian Brat
Journal of Cancer Research and Clinical Oncology.2023; 149(19): 17123. CrossRef

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Should We Perform Repeated Re-biopsy for the Detection of T790M Mutation?: Saerom Kim, Soo Han Kim, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2023;55(4):1190-1197. Published online April 17, 2023; DOI: https://doi.org/10.4143/crt.2023.320

Abstract PDF PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies.
Materials and Methods
We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
Results
Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation–positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I²=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I²=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies.
Conclusion
This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

Citations

Citations to this article as recorded by

Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] CrossRef
Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib
Taeyun Kim, Junsu Choe, Sun Hye Shin, Byeong-Ho Jeong, Kyungjong Lee, Hojoong Kim, Se-Hoon Lee, Sang-Won Um, Hamidreza Montazeri Aliabadi
PLOS ONE.2024; 19(9): e0310079. CrossRef
Rebiopsie tumorale : quand ? pour qui ? pourquoi ? comment ?
V. Fallet
Revue des Maladies Respiratoires Actualités.2023; 15(2): 2S121. CrossRef

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The Additive Impact of Transbronchial Cryobiopsy Using a 1.1-mm Diameter Cryoprobe on Conventional Biopsy for Peripheral Lung Nodules: Soo Han Kim, Jeongha Mok, Eun-Jung Jo, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2023;55(2):506-512. Published online November 1, 2022; DOI: https://doi.org/10.4143/crt.2022.1008

Abstract PDF Supplementary Material PubReader ePub

Purpose
The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs).
Materials and Methods
From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022.
Results
The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm²) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm², p < 0.001) and 1.9-mm forceps (3.7 mm², p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications.
Conclusion
Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Citations

Citations to this article as recorded by

Complete resolution of non-tuberculous mycobacterial pulmonary nodule following cryobiopsy: The first case report
Sung Joon Han, Chaeuk Chung, Dongil Park
Diagnostic Pathology.2025;[Epub] CrossRef
Transbronchial lung cryobiopsy for peripheral pulmonary lesions. A narrative review
Y. Tang, S. Tian, H. Chen, X. Li, X. Pu, X. Zhang, Y. Zheng, Y. Li, H. Huang, C. Bai
Pulmonology.2024; 30(5): 475. CrossRef
Transbronchial Tumor Ablation
Russell Miller, George Cheng
Current Pulmonology Reports.2024; 13(1): 103. CrossRef
Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study
Ching-Kai Lin, Sheng-Yuan Ruan, Hung-Jen Fan, Hao-Chun Chang, Yen-Ting Lin, Chao-Chi Ho
Respiratory Research.2024;[Epub] CrossRef
Next‐generation sequencing using tissue specimen collected with a 1.1 mm‐diameter cryoprobe in patients with lung cancer
Mi‐Hyun Kim, Soo Han Kim, Geewon Lee, Jeongha Mok, Min Ki Lee, Ju Sun Song, Jung Seop Eom
Respirology.2024; 29(4): 333. CrossRef
Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis
Soo Han Kim, Hyun Sung Chung, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Insu Kim, Jung Seop Eom
Cancer Research and Treatment.2024; 56(2): 464. CrossRef
Navigational bronchoscopy with tranbronchial cryobiopsy in differential diagnosis of peripheral pulmonary lesions
Ya.O. Chesalina, I.Yu. Shabalina, L.A. Semenova, I.V. Sivokozov
Pirogov Russian Journal of Surgery.2024; (6): 36. CrossRef
Advanced Bronchoscopic Diagnostic Techniques in Lung Cancer
Dongil Park
Tuberculosis and Respiratory Diseases.2024; 87(3): 282. CrossRef
Clinical utility of rapid on-site evaluation of brush cytology during bronchoscopy using endobronchial ultrasound with a guide sheath
Kazuhiro Nishiyama, Kei Morikawa, Shotaro Kaneko, Makoto Nishida, Aya Matsushima, Yoshihiro Nishi, Yu Numata, Yusuke Shinozaki, Hajime Tsuruoka, Hirotaka Kida, Hiroshi Handa, Naoki Shimada, Chie Okawa, Nobuyuki Ohike, Junki Koike, Masamichi Mineshita
Scientific Reports.2024;[Epub] CrossRef
Bronchial branch tracing navigation in ultrathin bronchoscopy-guided radial endobronchial ultrasound for peripheral pulmonary nodule
Sze Shyang Kho, Shirin Hui Tan, Swee Kim Chan, Chan Sin Chai, Siew Teck Tie
BMC Pulmonary Medicine.2024;[Epub] CrossRef
The diagnosis of peripheral lung lesions: transbronchial biopsy using a radial probe endobronchial ultrasound
Jung Seop Eom
Journal of the Korean Medical Association.2023; 66(3): 166. CrossRef
Clinical outcomes of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe for peripheral lung lesions - A prospective pilot study
Soo Han Kim, Jeongha Mok, Saerom Kim, Wan Ho Yoo, Eun-Jung Jo, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jung Seop Eom
Respiratory Medicine.2023; 217: 107338. CrossRef

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Metabolic Burden Measured by ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Is a Prognostic Factor in Patients with Small Cell Lung Cancer: Mi-Hyun Kim, Ji Seok Lee, Jeong Ha Mok, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Seong-Jang Kim, Min Ki Lee; Cancer Res Treat. 2014;46(2):165-171. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.165

Abstract PDF PubReader ePub

Purpose

Evidence regarding the usefulness of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in predicting the prognosis of non-small cell lung cancer is increasing. However, data on small cell lung cancer (SCLC) are scarce. The aim of this study was to evaluate the prognostic value of metabolic parameters measured using ¹⁸F-FDG PET/CT in patients with SCLC.

Materials and Methods

We conducted a retrospective review of 114 patients with pathologically proven SCLC (26 cases of limited disease and 88 cases of extensive disease) who underwent pretreatment ¹⁸F-FDG PET/CT. The maximal SUV (SUV_max) was used quantitatively for determination of FDG PET activity. The SUV_max of the primary tumor (primary SUV_max), the sum of SUV_max values of malignant lesions (SUV_sum), and the mean SUV_max of malignant lesions were calculated.

Results

The patient population was subdivided using a median SUV_sum value of 24.6. High SUV_sum showed a significant association with known factors for poor prognosis, including higher neuron-specific enolase (p=0.010), CYFRA 21-1 (p=0.014), and extensive disease status (p=0.007). Patients with high SUV_sum had significantly shorter median overall survival (6.6 months vs. 13.0 months, p<0.001) and progression-free survival (5.2 months vs. 8.0 months, p<0.001) than patients with low SUV_sum. Results of multivariate analysis showed that SUV_sum, chemotherapy cycles, and the response to first-line treatment were significant prognostic factors of survival. In contrast, mean SUV_max and primary SUV_max were not significant predictors of survival.

Conclusion

In this study, metabolic burden represented by SUV_sum from pretreatment ¹⁸F-FDG PET/CT was an independent prognostic factor in patients with SCLC.

Citations

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Prognostic value of metabolic parameters on baseline 18F-FDG PET/CT in small cell lung cancer
Mine ARAZ, Cigdem SOYDAL, Elgin ÖZKAN, Elif SEN, Demet NAK, Ozlem N. KUCUK, Ugur GÖNÜLLÜ, K. Metin KIR
The Quarterly Journal of Nuclear Medicine and Molecular Imaging.2022;[Epub] CrossRef
Predictive Factors of Complete Tumor Response to First Line Chemotherapy in Patients with Extensive-stage Small Cell Lung Cancer
Eyyüp Çavdar, Yakup İriağaç, Abdullah Sakin, Erdoğan Selçuk Şeber
Bagcilar Medical Bulletin.2022; 7(2): 130. CrossRef
Prognostic Value of 18F–FDG–PET Parameters in Patients with Small Cell Lung Cancer: A Meta-Analysis and Review of Current Literature
Tine Nøhr Christensen, Per Kragh Andersen, Seppo W. Langer, Barbara Malene Bjerregaard Fischer
Diagnostics.2021; 11(2): 174. CrossRef
Prognostic significance of neutrophil/lymphocyte ratio (NLR) and correlation with PET–CT metabolic parameters in small cell lung cancer (SCLC)
Cem Mirili, Isa Burak Guney, Semra Paydas, Gulsah Seydaoglu, Tuba Korkmaz Kapukaya, Ali Ogul, Serkan Gokcay, Mahmut Buyuksimsek, Abdullah Evren Yetisir, Bilgin Karaalioglu, Mert Tohumcuoglu
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Pretreatment metabolic parameters measured by 18F-FDG-PET to predict the outcome of first-line chemotherapy in extensive-stage small-cell lung cancer
Xiaozhou Yu, Yanjia Zhu, Jian Wang, Xiuyu Song, Lei Zhu, Xiaoyuan Men, Xiaofeng Li, Dong Dai, Wengui Xu
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Meryem Aktan, Mehmet Koc, Gul Kanyilmaz, Berrin Benli Yavuz
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The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer
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A. Patnaik, L.J. Appleman, A.W. Tolcher, K.P. Papadopoulos, M. Beeram, D.W. Rasco, G.J. Weiss, J.C. Sachdev, M. Chadha, M. Fulk, S. Ejadi, J.M. Mountz, M.T. Lotze, F.G.S. Toledo, E. Chu, M. Jeffers, C. Peña, C. Xia, S. Reif, I. Genvresse, R.K. Ramanathan
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Frederic Sampedro, Anna Domenech, Sergio Escalera, Ignasi Carrió
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Metabolic tumor burden is associated with major oncogenomic alterations and serum tumor markers in patients with resected pancreatic cancer
Si Shi, Shunrong Ji, Yi Qin, Jin Xu, Bo Zhang, Wenyan Xu, Jiang Liu, Jiang Long, Chen Liu, Liang Liu, Quanxing Ni, Xianjun Yu
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Interpretation and Prognostic Value of Positron Emission Tomography-Computed Tomography After Induction Chemotherapy With or Without Radiation in IIIA-N2 Non-small Cell Lung Cancer Patients Who Receive Curative Surgery
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Prognostic Factors in Patients Treated with 223Ra: The Role of Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT in Predicting Overall Survival
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Journal of Nuclear Medicine.2015; 56(10): 1507. CrossRef

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Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer: Min-Ho Park, Deok-Hwan Yang, Mi-Hyun Kim, Jae-Hong Jang, Yoon-Young Jang, Youn-Kyung Lee, Chun-Ji Jin, Than Nhan Nguyen Pham, Truc Anh Nguyen Thi, Mi-Seon Lim, Hyun-Ju Lee, Cheol Yi Hong, Jung-Han Yoon, Je-Jung Lee; Cancer Res Treat. 2011;43(1):56-66. Published online March 31, 2011; DOI: https://doi.org/10.4143/crt.2011.43.1.56

Abstract PDF PubReader ePub

PURPOSE
Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (alpha DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
MATERIALS AND METHODS
alphaDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed alphaDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
RESULTS
The alphaDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the alphaDC1s were loaded with tumor antigens. The alphaDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by alphaDC1s loaded with apoptotic MCF-7 cells.
CONCLUSION
Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.

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João Constantino, Célia Gomes, Amílcar Falcão, Maria T. Cruz, Bruno M. Neves
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