Nat Immunol
March 2025
Most patients with colorectal cancer do not achieve durable clinical benefits from immunotherapy, underscoring the existence of alternative immunosuppressive mechanisms. Here we found that activation of the lactate receptor HCAR1 signaling pathway induced the expression of chemokines CCL2 and CCL7 in colorectal tumor cells, leading to the recruitment of immunosuppressive CCR2 polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to the tumor microenvironment. Ablation of Hcar1 in mice with colorectal tumors significantly decreased the abundance of tumor-infiltrating CCR2 PMN-MDSCs, enhanced the activation of CD8 T cells and, consequently, reduced tumor burden.
View Article and Find Full Text PDFCancer Commun (Lond)
December 2024
The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk.
View Article and Find Full Text PDFD2 surgery followed by adjuvant chemotherapy has been established as the standard of care for patients with locally advanced gastric cancer in Asian countries. However, its efficacy is still unsatisfactory, especially for pathological N3 disease. The RACING trial is a randomized, multicenter, Phase III trial designed to compare the efficacy and safety of chemotherapy alone versus chemotherapy in combination with PD-1 inhibitor and radiotherapy in patients with pN3 gastric or gastroesophageal junction adenocarcinoma.
View Article and Find Full Text PDFBackground: Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic-based score (Rad-score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules.
Methods: Retrospective data from two institutions (July 10, 2006-September 24, 2015) was used to develop and validate the Rad-score for distinguishing lung nodule malignancy.
Background: The skeletal muscle index (SMI) can serve as a surrogate for a patient's nutritional status, which is associated with treatment toxicity. This study aims to investigate the potential of baseline skeletal muscle radiomics features to predict gastrointestinal toxicity of neoadjuvant chemoradiotherapy for rectal cancer.
Methods: A total of 214 rectal cancer patients (115, 49 and 50 in the training, internal and external validation set, respectively) who underwent neoadjuvant pelvic radiotherapy with capecitabine and irinotecan were retrospectively identified.
Background: The watch-and-wait (W&W) strategy is a novel treatment option for patients with rectal cancer who have a strong desire for organ preservation. The study aimed to explore the long-term outcomes of the W&W strategy in a large cohort of rectal cancer patients who achieved a clinical complete response (cCR) after consolidation total neoadjuvant therapy (TNT), and to compare with patients who achieved a pathological complete response (pCR) after radical surgery.
Methods: The W&W group comprised patients who were assessed as having a cCR after consolidation TNT and adopted the W&W strategy.
Background: Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients.
View Article and Find Full Text PDFPangenomic study might improve the completeness of human reference genome (GRCh38) and promote precision medicine. Here, we use an automated pipeline of human pangenomic analysis to build gastric cancer pan-genome for 185 paired deep sequencing data (370 samples), and characterize the gene presence-absence variations (PAVs) at whole genome level. Genes ACOT1, GSTM1, SIGLEC14 and UGT2B17 are identified as highly absent genes in gastric cancer population.
View Article and Find Full Text PDFBMC Cancer
June 2022
Background: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress.
View Article and Find Full Text PDFMetastatic pancreatic cancer remains a major clinical challenge, emphasizing the urgent need for the exploitation of novel therapeutic approaches with superior response. In this study, we demonstrate that the aberrant activation of prostaglandin E (PGE) receptor 4 (EP4) is a pro-metastatic signal in pancreatic cancer. To explore the therapeutic role of EP4 signaling, we developed a potent and selective EP4 antagonist L001 with single-nanomolar activity using a panel of cell functional assays.
View Article and Find Full Text PDFBackground: Substantial evidence has demonstrated that tumor-infiltrating lymphocytes (TILs) are correlated with patient prognosis. The TIL-based immune score (IS) affects prognosis in various cancers, but its prognostic impact in gastric cancer (GC) patients treated with adjuvant chemoradiotherapy remains unclear.
Methods: A total of 101 GC patients who received chemoradiotherapy after gastrectomy were retrospectively analyzed in this study.
Objective: The aim of this study was to investigate the role of nutritional factors in predicting radiotherapy-associated toxicities for gastric cancer patients.
Methods: A total of 285 gastric cancer patients who underwent radiotherapy in our hospital (Fudan University Shanghai Cancer Center) between 2010 and 2017 were included in this retrospective study. Nutritional status assessment included body weight loss (BWL), body mass index (BMI), serum albumin, nutrition risk screening 2002(NRS-2002), patient-generated subjective global assessment(PG-SGA) and nutritional risk index (NRI).
Background: The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer.
Methods: This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution.
Purpose: Although adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT that of postoperative CRT for resectable or potentially resectable gastric cancer.
View Article and Find Full Text PDFAnn Transl Med
September 2020
Background: Radiation enteritis is common in cancer patients with abdominal and pelvic malignant tumors that have received radiotherapy. Regeneration of intestinal stem cells is a critical process for intestine self-repairing post-irradiation. In this study, we attempted to find out the molecules that promote the regeneration of intestinal stem cells to repair the irradiation damage.
View Article and Find Full Text PDFAnticancer Agents Med Chem
June 2021
Background: Colon cancer is one of the major causes of morbidity and mortality worldwide. Cycle inhibiting factors (Cifs) have been shown to deamidate Nedd8, resulting in cell cycle arrest.
Objective: To determine the antitumor effect of Cifs on colon cancer by using attenuated Salmonella typhimurium VNP20009.
Background And Purpose: This study aims to investigate changes in body composition during adjuvant chemoradiotherapy (CRT) quantitatively and visually in patients with gastric cancer and evaluate the correlation of the changes with survival and toxicity.
Materials And Methods: A total of 182 gastric cancer patients who underwent surgery and adjuvant CRT were included. CT images at the level of the third lumbar vertebra (L3) were analyzed to assess the areas of muscles.
Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors.
View Article and Find Full Text PDFThe human reference genome is still incomplete, especially for those population-specific or individual-specific regions, which may have important functions. Here, we developed a HUman Pan-genome ANalysis (HUPAN) system to build the human pan-genome. We applied it to 185 deep sequencing and 90 assembled Han Chinese genomes and detected 29.
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