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Small-cell lung cancer (SCLC) is an aggressive malignancy with immunosuppressive tumor microenvironment limiting immunotherapy efficacy. Here, we present a protocol to assess T cell activation and the ability of lurbinectedin to enhance anti-tumor responses using in vitro co-cultures of SCLC cells and human CD8 T cells. We describe steps for cell seeding, treatment, co-culture setup, and assessing cell viability. This protocol provides a platform to study anti-tumor T cell responses and develop new SCLC therapies. For complete details on the use and execution of the protocol, please refer to Chakraborty et al..
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022692 | PMC |
http://dx.doi.org/10.1016/j.xpro.2025.103767 | DOI Listing |
Signal Transduct Target Ther
September 2025
State Key Laboratory of Molecular Oncology & Department of Medical Oncology & Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor strongly associated with exposure to tobacco carcinogens, is characterized by early dissemination and dismal prognosis with a five-year overall survival of less than 7%. High-frequency gain-of-function mutations in oncogenes are rarely reported, and intratumor heterogeneity (ITH) remains to be determined in SCLC. Here, via multiomics analyses of 314 SCLCs, we found that the ASCL1/MKI67 and ASCL1/CRIP2 clusters accounted for 74.
View Article and Find Full Text PDFRadiother Oncol
September 2025
Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, Germany. Electronic address:
Background: Radiotherapy (RT) is an essential part of small-cell lung cancer (SCLC) treatment. It can however deplete circulating lymphocytes, impairing systemic immune surveillance and potentially reducing the efficacy of immune checkpoint inhibitors (ICIs). The Effective Dose to Immune Cells (EDIC) quantifies RT-induced immune suppression and has been linked to survival in non-small cell lung cancer (NSCLC), but its prognostic significance in SCLC remains unclear.
View Article and Find Full Text PDFOncol Ther
September 2025
Internal Medicine III, Wakayama Medical University, Kimiidera, Wakayama, 811-1, Japan.
Introduction: Tarlatamab is a bispecific T-cell engager (BiTE) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented.
View Article and Find Full Text PDFMol Cancer Ther
September 2025
Princess Margaret Cancer Centre, Toronto, ON, Canada.
Small cell lung cancer (SCLC) is an aggressive malignancy, with most patients presenting with prognostically poor extensive-stage disease. Limited progress in standard care stresses the urgent need for novel therapies. Radiotherapy offers some survival benefit for selected SCLC patients but could be enhanced with radiosensitizers.
View Article and Find Full Text PDFCell Commun Signal
August 2025
Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, 75080, USA.
Background: Cancer cells within tumors exhibit a wide range of phenotypic states driven by non-genetic mechanisms, such as epithelial-to-mesenchymal transition (EMT), in addition to extensively studied genetic alterations. Conversions among cancer cell states can result in intratumoral heterogeneity which contributes to metastasis and development of drug resistance. However, mechanisms underlying the initiation and/or maintenance of such phenotypic plasticity are poorly understood.
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