Immune phenotypic linkage between colorectal cancer and liver metastasis

The tumor microenvironment (TME) is connected to immunotherapy responses, but it remains unclear how cancer cells and host tissues differentially influence the immune composition within TME. Here, we performed single-cell analyses for autologous samples from liver metastasized colorectal cancer to disentangle factors shaping TME. By aligning CD45+ cells across different tissues, we classified exhausted CD8+ T cells (Texs) and activated regulatory T cells as M-type, whose phenotypes were associated with the malignancy, while natural killer and mucosal-associated invariant T cells were defined as N-type, whose phenotypes were associated with the niche. T cell receptor sharing between Texs in primary and metastatic tumors implicated the presence of common peripheral non-exhausted precursors. For myeloid cells, a subset of dendritic cells (DC3s) and SPP1+ macrophages were M-type, and the latter were predominant in liver metastasis, indicating its pro-metastasis role. Our analyses bridge immune phenotypes of primary and metastatic tumors, thereby helping to understand the tumor-specific contexture and identify the pro-metastasis components. [Display omitted] •Immune cell phenotypic linkage with colorectal cancer and liver metastasis depicted•Malignancy-associated exhausted and regulatory T cells show diverse TCR dependency•SPP1+ TAMs are malignancy associated and are linked to liver metastasis•DCs are mainly associated with host organ except a malignancy-associated DC3 subset Liu et al. reveal the roles of malignancy and host-organ contexture in shaping immune infiltrates within a tumor microenvironment based on single-cell phenotypic alignment of colorectal cancer and the autologous liver metastasis