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J. Immunother. Cancer, 16 February 2025 | https://doi.org/10.1136/ jitc-2024-010455
Blood TCTP as a potential biomarker associated with immunosuppressive features and poor clinical outcomes in metastatic gastric cancer
Hyung-Don Kim1, Seyoung Jung2, Yeong Hak Bang1, Jiae Kim1, Hee Jeong Kim1, Hyung Eun Lee1, Jaewon Hyung1, Changhoon Yoo1, Won-Tae Kim3, Myeong-Jin Yoon3, Hayoung Lee3, Jeong-Hyun Ryou3, Hyungsu Jeon3, Hideyuki Yanai4, Jeong Seok Lee2, Gwanghee Lee3 and Min-Hee Ryu1
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (the Republic of)
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea (the Republic of)
3Boostimmune, Seoul, Korea (the Republic of)
4Department of Inflammology, The University of Tokyo, Bunkyo-ku, Japan
H-DK and SJ are joint first authors.
Correspondence to Professor Min-Hee Ryu; Dr Gwanghee Lee
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (the Republic of)
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea (the Republic of)
3Boostimmune, Seoul, Korea (the Republic of)
4Department of Inflammology, The University of Tokyo, Bunkyo-ku, Japan
H-DK and SJ are joint first authors.
Correspondence to Professor Min-Hee Ryu; Dr Gwanghee Lee
Abstract
Background No established biomarker exists for specific myeloid cell populations or in gastric cancer. This study aimed to explore the prognostic and immunological relevance of plasma translationally controlled tumor protein (TCTP) in patients with advanced gastric cancer treated with an immune checkpoint inhibitor and/or cytotoxic chemotherapy.
Methods Plasma samples were prospectively collected from the cohorts of patients with gastric cancer treated with first-line fluoropyrimidine plus platinum chemotherapy (n=143, cohort 1) and third-line nivolumab (n=165, cohort 2). Plasma TCTP levels were quantified using ELISA, and multiplex proteomic analysis (Olink) was conducted to assess expression levels of immune-related proteins. External single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics datasets were employed to validate the findings.
Results Patients with high plasma TCTP levels (TCTP-high group) exhibited poor progression-free survival (PFS) and overall survival (OS) with first-line chemotherapy compared with those with low levels (TCTP-low group) in cohort 1 (HR: 1.73 for PFS; 1.77 for OS). In the TCTP-high group, proteins associated with immunosuppressive myeloid cells, angiogenesis, and immune exclusion of T/natural killer (NK) cell function were upregulated, whereas proteins involved in T-cell activation/exhaustion were significantly upregulated in the TCTP-low group. scRNA-seq analyses identified a myeloid subset with high TPT1 (encoding TCTP) expression and TCTP-related molecules, enriched with inhibitory myeloid inflammation gene signatures and providing inhibitory signals to T/NK cells (Macrophage-chemokine). Spatial transcriptomics analyses revealed a tumor-cell-enriched cluster co-localized with the Macrophage-chemokine subset, which exhibited the highest TPT1 expression and a positive correlation between its abundance and average TPT1 levels. In nivolumab-treated patients (cohort 2), the high TCTP group was associated with poor survival outcomes (HR: 1.39 for PFS; 1.47 for OS).
Conclusions Plasma TCTP is a prognostic biomarker, reflecting clinically relevant immunosuppressive myeloid signals in patients with gastric cancer.
Methods Plasma samples were prospectively collected from the cohorts of patients with gastric cancer treated with first-line fluoropyrimidine plus platinum chemotherapy (n=143, cohort 1) and third-line nivolumab (n=165, cohort 2). Plasma TCTP levels were quantified using ELISA, and multiplex proteomic analysis (Olink) was conducted to assess expression levels of immune-related proteins. External single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics datasets were employed to validate the findings.
Results Patients with high plasma TCTP levels (TCTP-high group) exhibited poor progression-free survival (PFS) and overall survival (OS) with first-line chemotherapy compared with those with low levels (TCTP-low group) in cohort 1 (HR: 1.73 for PFS; 1.77 for OS). In the TCTP-high group, proteins associated with immunosuppressive myeloid cells, angiogenesis, and immune exclusion of T/natural killer (NK) cell function were upregulated, whereas proteins involved in T-cell activation/exhaustion were significantly upregulated in the TCTP-low group. scRNA-seq analyses identified a myeloid subset with high TPT1 (encoding TCTP) expression and TCTP-related molecules, enriched with inhibitory myeloid inflammation gene signatures and providing inhibitory signals to T/NK cells (Macrophage-chemokine). Spatial transcriptomics analyses revealed a tumor-cell-enriched cluster co-localized with the Macrophage-chemokine subset, which exhibited the highest TPT1 expression and a positive correlation between its abundance and average TPT1 levels. In nivolumab-treated patients (cohort 2), the high TCTP group was associated with poor survival outcomes (HR: 1.39 for PFS; 1.47 for OS).
Conclusions Plasma TCTP is a prognostic biomarker, reflecting clinically relevant immunosuppressive myeloid signals in patients with gastric cancer.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-03-04)
- 국내 연구진
- 의약학 > 응용의학
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