BIOPIC Zhang Zemin/Ren Xianwen's research group and collaborators analyze the potential influencing factors of tumor microenvironment formation

On March 17, 2022, Prof.

Tumor microenvironment (TME) characteristics are intrinsically linked to the efficacy of cancer immunotherapy, and TME characteristics can affect cancer progression and metastasis

Comparative analysis of TME from different cancer types and different patients cannot answer the above questions, because it cannot exclude the influence of differences in tumor cells and different genetic backgrounds of different patients

The researchers collected 101 matched samples from 17 untreated colorectal cancer liver metastases (CRLM) patients, including primary colorectal cancer and paracancer, liver metastases and paracancer, mesenteric lymph nodes, and peripheral blood.

Figure 1 Project research plan and main conclusions

By comparing the infiltration of immune cells in CRC and HCC patients, the researchers found that the infiltration of immune cells may be related to the pathological state (tumor/paracancerous tissue) and the organ in which it resides (intestine/liver): Treg-CTLA4 , Tex-LAYN and Mph-C1QC were more enriched in tumor tissues than adjacent tumors; MAIT cells tended to be enriched in liver, while IEL cells tended to be enriched in intestine

Figure 2 Principle of Pheno Aligner method

Among CD8 ⁺ T cells, exhausted T cells (Tex) are identified as M class, i.

Figure 3 The process of CD8 ⁺ T cells infiltrating different tumor sites in the tumor immune cycle

Among CD4+ T cells, four subclasses were identified as M class by Pheno Aligner and found in combination with TCR information, among which Treg-CTLA4 and Th1-like cells, like Tex cells, showed a TCR-dependent pattern, while Treg-IL10 and Th17 cells However, the TCR-independent pattern showed no shared TCR sequences between the primary and metastatic tumor sites, revealing that Treg-CTLA4 and Th1-like cells at different tumor sites were derived from the same precursor cells, while Treg-IL10 and Th17 cells are recruited by tumor cells from different origins

Dendritic cells (DCs) are one of the key cell subsets in antigen-specific immune responses.

In addition, the researchers found three groups of tumor-associated macrophages (TAMs) with high expression of SPP1, C1QC, and MKI67, respectively, and all three groups were identified as M class

In conclusion, this study outlines the immune atlases of various tissues of patients with colorectal cancer liver metastases, reveals the influence of tumor cell characteristics and resident organs on different immune cell phenotypes, and provides a framework for in-depth understanding of immune characteristics between different cancer types.

Liu Yedan and Zhang Qiming are the co-first authors of the paper