Spatial immune archetypes in gastric and colorectal cancer: a proposed conceptual framework for immunotherapy resistance and therapeutic remodeling

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Gastric and colorectal cancers are major contributors to global cancer mortality, with most patients exhibiting primary resistance to immunotherapy.
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Immunotherapy outcomes are influenced by spatial immune archetypes, which dictate immune exclusion and local activation rather than lymphocyte abundance alone.
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Four spatial immune archetypes are proposed: stromal-excluded barrier niche, myeloid-suppressive metabolic niche, inflamed lymphoid-reactive niche, and epithelial-immune interface niche.
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Tissue-specific anatomical constraints and microbial ecologies shape the prevalence of these spatial archetypes in gastric and colorectal cancers.
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The review emphasizes the need for archetype-guided spatial biomarkers and microenvironment-remodeling strategies to improve immunotherapy efficacy in MSS/pMMR cancers.

Frontiers In Immunology

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