Spatiotemporal Antigen Accessibility Theory (SAAT): A unifying framework for immune failure in hepatobiliary–pancreatic cancers
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2026
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| _version_ | 1866902297736380416 |
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| author | Lee, Li Chung |
| author_facet | Lee, Li Chung |
| contents | <p><span>Hepatobiliary and pancreatic malignancies remain largely refractory to immunotherapy, reflecting a persistent inability of anti-tumour immune responses to achieve effective tumour control. This limitation suggests that current frameworks centred on immune suppression or T cell dysfunction are insufficient to explain immune failure in these cancers. Here, I propose the <strong><span>Spatiotemporal Antigen Accessibility Theory (SAAT)</span></strong>, which conceptualizes anti-tumour immunity as a process constrained by both the spatial accessibility of antigens and the temporal alignment of immune activation.</span></p> <p><span>Within this framework, antigen accessibility is not an intrinsic property of tumours but a dynamically regulated condition shaped by tissue architecture, lymphatic function and transient inflammatory states. Tumour-involved lymph nodes may function as <strong><span>antigen source reservoirs (PAR)</span></strong>, providing the substrate for antigen generation without accessible antigenic identity. In parallel, stromal structure and interstitial pressure impose spatial constraints on antigen exchange and immune cell trafficking, conceptualized as <strong><span>lymphatic pressure balance environments</span></strong>. Furthermore, effective immune engagement depends on a transient window of <strong><span>functional state permissiveness</span></strong>, during which antigen availability and immune activation are temporally synchronized.</span></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_20054439 |
| institution | Zenodo |
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| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Spatiotemporal Antigen Accessibility Theory (SAAT): A unifying framework for immune failure in hepatobiliary–pancreatic cancers Lee, Li Chung <p><span>Hepatobiliary and pancreatic malignancies remain largely refractory to immunotherapy, reflecting a persistent inability of anti-tumour immune responses to achieve effective tumour control. This limitation suggests that current frameworks centred on immune suppression or T cell dysfunction are insufficient to explain immune failure in these cancers. Here, I propose the <strong><span>Spatiotemporal Antigen Accessibility Theory (SAAT)</span></strong>, which conceptualizes anti-tumour immunity as a process constrained by both the spatial accessibility of antigens and the temporal alignment of immune activation.</span></p> <p><span>Within this framework, antigen accessibility is not an intrinsic property of tumours but a dynamically regulated condition shaped by tissue architecture, lymphatic function and transient inflammatory states. Tumour-involved lymph nodes may function as <strong><span>antigen source reservoirs (PAR)</span></strong>, providing the substrate for antigen generation without accessible antigenic identity. In parallel, stromal structure and interstitial pressure impose spatial constraints on antigen exchange and immune cell trafficking, conceptualized as <strong><span>lymphatic pressure balance environments</span></strong>. Furthermore, effective immune engagement depends on a transient window of <strong><span>functional state permissiveness</span></strong>, during which antigen availability and immune activation are temporally synchronized.</span></p> |
| title | Spatiotemporal Antigen Accessibility Theory (SAAT): A unifying framework for immune failure in hepatobiliary–pancreatic cancers |
| url | https://doi.org/10.5281/zenodo.20054439 |