Top 5 Papers
#1
Source: Cancer Immunology Research | Authors: Lin NY, Machiyama H, Kawazoe A, Shitara K, Nishikawa H, Koyama S, et al. | Published: April 27, 2026
Score: 9/20 — Base 6 (Cancer Immunol Res) + Phase II trial data (+2) + Biomarker-guided/precision (+1)
Translational analysis from the EPOC1706 clinical trial of lenvatinib plus pembrolizumab in advanced gastric cancer. Longitudinal immunoprofiling of paired tumor samples revealed that lenvatinib selectively reduced CD206+CD163+ immunosuppressive macrophages in the TME and increased antitumor immunity. Patients with abundant immunosuppressive macrophage infiltration (>440/mm²) had favorable responses to combination therapy — 8 of 9 responded — while none of 8 such patients responded to PD-1 monotherapy. Mechanistically, lenvatinib inhibited PDGFRα/FGFR-dependent p38 MAPK and AKT signaling in immunosuppressive macrophages, triggering ER stress and apoptosis. This identifies immunosuppressive macrophage abundance as a predictive biomarker for patient stratification in anti-PD-1 combination therapy.
Post angle: EPOC1706 reveals the mechanism: lenvatinib kills immunosuppressive macrophages via PDGFRα/FGFR → ER stress. 8/9 macrophage-rich tumors responded to combo vs 0/8 on IO alone. A predictive biomarker for GC. #GastricCancer #Immunotherapy #PrecisionMedicine #GIOnc
#2
Source: Nature Cell Biology | Authors: Kozlova N, Cruz KA, Doh HM, Scully R, Muranen T, et al. | Published: April 27, 2026
Score: 8/20 — Base 7 (Nature Cell Biology) + Biomarker-guided/precision (+1)
This study reveals an unexpected link between CAF-secreted extracellular matrix proteins and enhanced DNA repair in PDAC. NDRG1 was identified as a key mediator that senses ECM signals via adhesion receptors and SGK kinase, physically associates with replication forks, maintains DNA replication, resolves stalled forks caused by chemotherapies, and reduces R-loops (RNA-DNA hybrids causing genomic instability). High NDRG1 expression in PDAC tumors correlates with poor disease-specific survival and poor chemotherapy response. This mechanistically links tumor stroma to replication fork homeostasis and explains a major resistance mechanism.
Post angle: CAFs aren't just structural — they're actively protecting PDAC cancer cells from chemo damage. NDRG1 senses ECM signals and resolves DNA replication stress. High NDRG1 = poor survival. The stroma fights back. #PDAC #CAFs #DNARepair #NatureCellBiology #GIOnc
#3
Source: British Journal of Cancer | Authors: Gu Y, Wang J, Ling Z, Xu J, et al. | Published: April 28, 2026
Score: 8/20 — Base 6 (British Journal of Cancer) + Retrospective (+1) + Biomarker-guided/precision (+1)
Analysis of 1,273 gastric cancer patients across six independent cohorts (ZSHS, TCGA, ACRG, SMC, MSKCC, ZSHS NGS). CCNE1 gain (amplification or Cyclin E1 overexpression) affects >10% of patients and defines a therapy-refractory subtype beyond the epithelial-mesenchymal framework. These tumors retain E-cadherin positivity but exhibit aggressive proliferative behavior and an immune-desert phenotype with reduced lymphocyte infiltration, impaired cytotoxicity, increased M2 macrophage polarization, and elevated TGF-β. CCNE1 gain was associated with poor prognosis and reduced response to adjuvant chemotherapy, HER2-targeted therapy, anti-angiogenic agents, and PD-1 blockade.
Post angle: CCNE1 gain in gastric cancer: >10% of patients, resistant to everything — chemo, HER2, anti-angiogenics, AND IO. Why? Immune desert + M2 macrophage dominance. A clinic-ready biomarker defining an unmet need. #GastricCancer #CCNE1 #ImmuneDesert #GIOnc
#4
Source: Signal Transduction and Targeted Therapy | Authors: Guo X, Liu Y, Li T, Yu J, Gao S, Hao J, et al. | Published: April 28, 2026
Score: 7/20 — Base 6 (Signal Transduct Target Ther) + Biomarker-guided/precision (+1)
Using scRNA-seq on specimens from PDAC patients treated with surufatinib plus chemotherapy, researchers identified a distinct subset of damage-associated macrophages (DAMs) characterized by high GPR34 expression. GPR34+ macrophages respond to tissue damage by releasing lysophosphatidylserine (LysoPS), enhancing CXCL16 secretion and efferocytosis. This efferocytosis promotes MHC-I degradation via the macrophage lysosomal pathway, leading to CD8+ T cell exhaustion. Combining a GPR34 antagonist with chemotherapy and surufatinib significantly enhanced anti-tumor responses in preclinical models, identifying GPR34 as a promising immune therapeutic target in PDAC.
Post angle: scRNA-seq from surufatinib-treated PDAC reveals GPR34+ macrophages eating dead cells and degrading MHC-I → CD8 T cell exhaustion. GPR34 antagonist + surufatinib = enhanced anti-tumor immunity. A new combination target. #PDAC #Macrophages #Immunotherapy #GIOnc
#5
Source: BioDrugs | Authors: Sato Y, Yagi K, Ishigaki K, Fujishiro M, et al. | Published: April 27, 2026
Score: 7/20 — Base 5 (Other journal) + Retrospective/real-world (+1) + Biomarker-guided/precision (+1)
Retrospective nationwide analysis of Japan's C-CAT registry including 798 patients with gastric cancer and 114 with EGJ adenocarcinoma treated with nivolumab monotherapy. Genomic associations with nivolumab outcomes differed by tumor site. In gastric cancer, ASXL1 mutation was independently associated with longer TTF (HR 0.59), MSI-H with longer OS (HR 0.16), and CDH1 mutation with shorter OS (HR 1.51). In EGJ cancer, NTRK1 mutation correlated with longer TTF and MUTYH with shorter OS (HR 5.68). These site-specific genomic markers could guide rational immunotherapy decisions beyond MSI/PD-L1.
Post angle: 912 patients from Japan's C-CAT registry reveal site-specific genomic markers for PD-1 response. ASXL1 = benefit in gastric, CDH1 = poor OS. Different tumor sites need different biomarkers. #GastricCancer #GEJ #Genomics #PrecisionMedicine #GIOnc
Additional Papers of Interest
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European Radiology — TLNS score from CT imaging outperforms clinical N staging for ypN0 risk stratification in esophageal SCC after neoadjuvant immunochemotherapy; high TLNS patients benefit from adjuvant therapy (n=325, multicenter)
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Journal of Gastroenterology — scRNA-seq reveals TREM1+ myeloid cells engage CAFs via SPP1 signaling while CAFs reinforce immunosuppression via TGF-β; TREM1 inhibition reduces SPP1 and M2 polarization in CRC
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BMJ Open — Difference-in-differences analysis: gastric incidence -28%, CRC incidence -22%, liver cancer mortality -38% after organized screening implementation (1999-2021)
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Journal of Translational Medicine — Tissue-resident Limosilactobacillus reuteri modulates intratumoral arachidonic acid metabolism to enhance CD8+ T cell-mediated anti-PD1 response in CRC
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Journal for ImmunoTherapy of Cancer — FXa inhibitor rivaroxaban disrupts FXa/PAR-2/PD-L1 axis, restoring T cell function; proposed as core adjuvant in 'local-targeted-immune' strategy for advanced HCC with PVTT
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