肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中重要的先天免疫细胞亚群，它们是调节肿瘤促进性炎症和肿瘤进展的关键调节因子。据证据表明，在癌症中TAM的数量显著增加，并且其中大部分TAM偏向于替代激活的M2表型。因此，这些TAM强烈推动了癌症的进展。第一型先天淋巴细胞（ILC1s）在肠道组织中数目众多，其特征是T-bet转录因子的表达和干扰素（IFN）-γ的分泌，IFN-γ促进巨噬细胞极化为经典激活的抗肿瘤M1表型。然而，这两种细胞亚群在结肠癌中的关系尚不清楚。本研究使用流式细胞术确定AOM/DSS诱导的结肠癌小鼠模型中结肠癌组织和癌旁组织中M1样巨噬细胞、M2样巨噬细胞和ILC1s的百分比。此外，我们分离了ILC1s，并生成骨髓源巨噬细胞来分析这些细胞在体外共培养时的相互作用。此外，我们在体内进行了ILC1s的移植或抑制实验，以探索ILC1s对肿瘤浸润巨噬细胞和肿瘤生长的影响。我们发现结肠癌组织中M1样巨噬细胞和ILC1s的百分比降低，并且这些细胞群体呈正相关。体外实验表明，ILC1s促进巨噬细胞向经典活化的M1样表型极化，而这种效应可以被抗IFN-γ抗体阻断。体内实验结果显示，给予Group 1先天淋巴细胞抑制剂抗-NK1.1抗体可以减少MC38肿瘤细胞移植小鼠的肿瘤组织中M1样巨噬细胞数量并促进肿瘤生长，而ILC1s的移植则抑制肿瘤并增加MC38肿瘤细胞移植小鼠中M1样巨噬细胞的百分比。我们的研究初步证明了ILC1s通过分泌IFN-γ促进M1样巨噬细胞的活化，并抑制结肠癌的进展，这可能为结肠癌的免疫治疗提供了新的思路。© 2023. BioMed Central Ltd., part of Springer Nature.

Tumor-associated macrophages (TAMs) are an important subset of innate immune cells in the tumor microenvironment, and they are pivotal regulators of tumor-promoting inflammation and tumor progression. Evidence has proven that TAM numbers are substantially increased in cancers, and most of these TAMs are polarized toward the alternatively activated M2 phenotype; Thus, these TAMs strongly promote the progression of cancer diseases. Type 1 innate lymphocytes (ILC1s) are present in high numbers in intestinal tissues and are characterized by the expression of the transcription factor T-bet and the secretion of interferon (IFN)-γ, which can promote macrophages to polarize toward the classically activated antitumor M1 phenotype. However, the relationship between these two cell subsets in colon cancer remains unclear.Flow cytometry was used to determine the percentages of M1-like macrophages, M2-like macrophages and ILC1s in colon cancer tissues and paracancerous healthy colon tissues in the AOM/DSS-induced mouse model of colon cancer. Furthermore, ILC1s were isolated and bone marrow-derived macrophages were generated to analyze the crosstalk that occurred between these cells when cocultured in vitro. Moreover, ILC1s were adoptively transferred or inhibited in vivo to explore the effects of ILC1s on tumor-infiltrating macrophages and tumor growth.We found that the percentages of M1-like macrophages and ILC1s were decreased in colon cancer tissues, and these populations were positively correlated. ILC1s promoted the polarization of macrophages toward the classically activated M1-like phenotype in vitro, and this effect could be blocked by an anti-IFN-γ antibody. The in vivo results showed that the administration of the Group 1 innate lymphocyte-blocking anti-NK1.1 antibody decreased the number of M1-like macrophages in the tumor tissues of MC38 tumor-bearing mice and promoted tumor growth, and adoptive transfer of ILC1s inhibited tumors and increased the percentage of M1-like macrophages in MC38 tumor-bearing mice.Our studies preliminarily prove for the first time that ILC1s promote the activation of M1-like macrophages by secreting IFN-γ and inhibit the progression of colon cancer, which may provide insight into immunotherapeutic approaches for colon cancer.© 2023. BioMed Central Ltd., part of Springer Nature.