Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling
Abstract Background Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon canc...
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BMC
2025-06-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14211-y |
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| author | Yaqi Wang Jiahua Lu Dandan Huang Pengju Chen Jingyi Shi Jie Cheng Jingbo Gan Ruifeng Li Jingxuan Xu Zhaoya Gao Xiaodong Wang Wensheng Huang Yanhui Yin Hebing Chen Jing Huang Cheng Li Jin Gu |
| author_facet | Yaqi Wang Jiahua Lu Dandan Huang Pengju Chen Jingyi Shi Jie Cheng Jingbo Gan Ruifeng Li Jingxuan Xu Zhaoya Gao Xiaodong Wang Wensheng Huang Yanhui Yin Hebing Chen Jing Huang Cheng Li Jin Gu |
| author_sort | Yaqi Wang |
| collection | DOAJ |
| description | Abstract Background Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon cancer who experienced explosive tumor growth. A clinical multidisciplinary team (MDT) collaborated with bioinformaticians to provide precise treatment and elucidate the biological mechanisms underpinning this growth. Methods A 28-year-old male patient diagnosed with colon cancer experienced explosive tumor growth. Peripheral bloods (PB) during immunotherapy were collected for immune cytokine analyses and flow cytometry assays on immune cell subsets. To further examine the underlying mechanisms of this explosive-growth, we conducted whole exome sequencing (WES) and RNA-sequencing (RNA-seq) of samples taken at different time points. Results The patient was diagnosed with Lynch syndrome. We implemented an immunotherapy and performed PB immune cytokine assays before, during, and after this therapy. Our observations suggested that immunotherapy may remodel interferon-gamma (IFN-γ) signaling and enhance T cell-mediated immune responses. By exploring explosive tumor growth mechanisms, we observed that tumors had significantly less insertion and deletion (INDEL) mutations and INDEL-derived neoantigens. Additionally, they had deficient antigen presentation functions as characterized by decreased IFN-γ signaling activity. Conclusions Neoantigen loss and decreased IFN-γ signaling activity contributed to explosive tumor growth in this patient. Recovered IFN-γ signaling may lead to effective immunotherapy outcomes. |
| format | Article |
| id | doaj-art-70faacd2a4a3470abe9a5315d2b560d2 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-70faacd2a4a3470abe9a5315d2b560d22025-08-20T03:10:38ZengBMCBMC Cancer1471-24072025-06-0125111410.1186/s12885-025-14211-yExplosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signalingYaqi Wang0Jiahua Lu1Dandan Huang2Pengju Chen3Jingyi Shi4Jie Cheng5Jingbo Gan6Ruifeng Li7Jingxuan Xu8Zhaoya Gao9Xiaodong Wang10Wensheng Huang11Yanhui Yin12Hebing Chen13Jing Huang14Cheng Li15Jin Gu16Department of Gastrointestinal Surgery, Peking University Shougang HospitalSchool of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking UniversityDepartment of Oncology, Peking University Shougang HospitalKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & InstituteDepartment of Pathology, School of Basic Medicine, Tongji Medical College, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and TechnologyPeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking UniversityInstitute for Immunology, Tsinghua UniversityKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & InstituteDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalDepartment of Oncology, Peking University Shougang HospitalDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, PUHSC Primary Immunodeficiency Research Center, Peking UniversityInstitute of Health Service and Transfusion MedicineDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, PUHSC Primary Immunodeficiency Research Center, Peking UniversitySchool of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking UniversityDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalAbstract Background Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon cancer who experienced explosive tumor growth. A clinical multidisciplinary team (MDT) collaborated with bioinformaticians to provide precise treatment and elucidate the biological mechanisms underpinning this growth. Methods A 28-year-old male patient diagnosed with colon cancer experienced explosive tumor growth. Peripheral bloods (PB) during immunotherapy were collected for immune cytokine analyses and flow cytometry assays on immune cell subsets. To further examine the underlying mechanisms of this explosive-growth, we conducted whole exome sequencing (WES) and RNA-sequencing (RNA-seq) of samples taken at different time points. Results The patient was diagnosed with Lynch syndrome. We implemented an immunotherapy and performed PB immune cytokine assays before, during, and after this therapy. Our observations suggested that immunotherapy may remodel interferon-gamma (IFN-γ) signaling and enhance T cell-mediated immune responses. By exploring explosive tumor growth mechanisms, we observed that tumors had significantly less insertion and deletion (INDEL) mutations and INDEL-derived neoantigens. Additionally, they had deficient antigen presentation functions as characterized by decreased IFN-γ signaling activity. Conclusions Neoantigen loss and decreased IFN-γ signaling activity contributed to explosive tumor growth in this patient. Recovered IFN-γ signaling may lead to effective immunotherapy outcomes.https://doi.org/10.1186/s12885-025-14211-yColorectal cancerExplosive tumor growthLynch syndromeImmunotherapy |
| spellingShingle | Yaqi Wang Jiahua Lu Dandan Huang Pengju Chen Jingyi Shi Jie Cheng Jingbo Gan Ruifeng Li Jingxuan Xu Zhaoya Gao Xiaodong Wang Wensheng Huang Yanhui Yin Hebing Chen Jing Huang Cheng Li Jin Gu Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling BMC Cancer Colorectal cancer Explosive tumor growth Lynch syndrome Immunotherapy |
| title | Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling |
| title_full | Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling |
| title_fullStr | Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling |
| title_full_unstemmed | Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling |
| title_short | Explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon-gamma (IFN-γ) signaling |
| title_sort | explosive tumor growth in a patient with colon cancer is associated with reduced neoantigen levels and decreased interferon gamma ifn γ signaling |
| topic | Colorectal cancer Explosive tumor growth Lynch syndrome Immunotherapy |
| url | https://doi.org/10.1186/s12885-025-14211-y |
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