ArticleNature communications2023
Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02788279 (A Phase III, Open-Label, Multicenter, Three-Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy vs. Regorafenib in Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Adenocarcinoma), which is not on this map. Cited by 31 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase III, Open-Label, Multicenter, Three-Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy vs. Regorafenib in Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Adenocarcinoma
Who cites it
31 citing papers in PubMed, 34 citations in OpenAlex.
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Piroctone olamine promotes BECN1 transcription and activates autophagy by targeting HDAC6 in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Dynamic transitioning between MAPK-driven and WNT-driven cell states drives intestinal cancer and shapes therapy response.Nature genetics · 2026Article
- TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer.World journal of oncology · 2026Article
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Membrane atg8ylation and autophagy in protection against Mycobacterium tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Insufficient Expression of the Autophagic Protein ATG16L1 Results in Accelerated Carcinogenesis Related to an Aberrant B Cell Response.Cancer reports (Hoboken, N.J.) · 2026Article
- RCC1 Domain-Containing Protein 1 Promotes Colon Cancer Malignant Progression by Activating Autophagy-Dependent WNT5A Secretion in Cancer-Associated Fibroblasts.Journal of the Royal Society of New Zealand · 2026Article
- Emerging KRAS G12D inhibitor in the treatment of digestive system tumors: opportunities and challenges.Translational gastroenterology and hepatology · 2026Review
- Nanomedicine delivery systems remodel the immunosuppressive microenvironment of colorectal cancer: synergistic strategies and mechanisms of targeted immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- ULK1 knockout suppresses pancreatic cancer progression by inhibiting autophagy and enhancing antitumor immunity.Experimental & molecular medicine · 2025Article
- Unveiling the clinical significance of RNA pseudouridine in colorectal cancer.Science China. Life sciences · 2025Article
- Atg16l1 and Xbp1 cooperatively protect from transcription-associated mutagenesis and small intestinal carcinogenesis.Oncogene · 2025Article
- New strategies to enhance the efficacy of PD-1/PD-L1 inhibitors in treating microsatellite stable colorectal cancer.Future oncology (London, England) · 2025Review
- Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025Review
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
- Intratumoral mycobiome heterogeneity influences the tumor microenvironment and immunotherapy outcomes in renal cell carcinoma.Science advances · 2025Article
- MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chromosome Missegregation Triggers Tumor Cell Pyroptosis and Enhances Anti-Tumor Immunotherapy in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microsatellite-stable colorectal cancer (MSS-CRC) is highly refractory to immunotherapy. Understanding tumor-intrinsic determinants of immunotherapy resistance is critical to improve MSS-CRC patient outcomes. Here, we demonstrate that high tumor expression of the core autophagy gene ATG16L1 is associated with poor clinical response to anti-PD-L1 therapy in KRAS-mutant tumors from IMblaze370 (NCT02788279), a large phase III clinical trial of atezolizumab (anti-PD-L1) in advanced metastatic MSS-CRC. Deletion of Atg16l1 in engineered murine colon cancer organoids inhibits tumor growth in primary (colon) and metastatic (liver and lung) niches in syngeneic female hosts, primarily due to increased sensitivity to IFN-γ-mediated immune pressure. ATG16L1 deficiency enhances programmed cell death of colon cancer organoids induced by IFN-γ and TNF, thus increasing their sensitivity to host immunity. In parallel, ATG16L1 deficiency reduces tumor stem-like populations in vivo independently of adaptive immune pressure. This work reveals autophagy as a clinically relevant mechanism of immune evasion and tumor fitness in MSS-CRC and provides a rationale for autophagy inhibition to boost immunotherapy responses in the clinic.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.