The tumor microenvironment (TME) is pivotal in cancer progression and the response to immunotherapy. A “hot” tumor typically contains immune cells that promote anti-tumor immunity, predicting positive prognosis. “Cold” tumors lack immune cells, suggesting a poor outlook across various cancers. Recent research has focused on converting “cold” tumors into “hot” tumors to enhance the success of immunotherapy. A prerequisite for the studies of the TME is an accurate knowledge of the cell populations of the TME. This study aimed to describe the immune TME of lung and colorectal cancer and melanoma, focusing on lymphoid and myeloid cell populations. We induced heterotopic immunocompetent tumors in C57BL/6 mice, using KP and LLC (Lewis lung carcinoma) cells for lung cancer, MC38 cells for colorectal cancer, and B16-F10 cells for melanoma. Immune cell infiltration was analyzed using multicolor flow cytometry in single-cell suspensions after tumor excision. KP cell tumors showed an abundance of neutrophils and eosinophils; however, they contained much less adaptive immune cells, while LLC cell tumors predominated in monocytes, neutrophils, and monocyte-derived dendritic cells. Monocytes and neutrophils, along with a significant T cell infiltration, were prevalent in MC38 tumors. Lastly, B16-F10 tumors were enriched in macrophages, while showing only moderate T cell presence. In conclusion, our data provide a detailed overview of the immune TME of various heterotopic tumors, highlighting the variabilities in the immune cell profiles of different tumor entities. Our data may be a helpful basis when investigating new immunotherapies, and thus, this report serves as a helpful tool for preclinical immunotherapy research design.
肿瘤微环境（TME）在癌症进展及免疫治疗反应中起着关键作用。"热"肿瘤通常含有促进抗肿瘤免疫的免疫细胞，预示着良好的预后；而"冷"肿瘤则缺乏免疫细胞，提示多种癌症的预后较差。近期研究致力于将"冷"肿瘤转化为"热"肿瘤以提高免疫治疗成功率。开展TME研究的前提是准确掌握其细胞群构成。本研究旨在描述肺癌、结直肠癌和黑色素瘤的免疫微环境特征，重点关注淋巴系和髓系细胞群。我们使用C57BL/6小鼠构建异位免疫活性肿瘤模型：采用KP细胞和LLC（路易斯肺癌）细胞建立肺癌模型，MC38细胞建立结直肠癌模型，B16-F10细胞建立黑色素瘤模型。通过肿瘤切除后制备单细胞悬液，采用多色流式细胞术分析免疫细胞浸润情况。KP细胞肿瘤显示中性粒细胞和嗜酸性粒细胞富集，但适应性免疫细胞含量显著较少；LLC细胞肿瘤以单核细胞、中性粒细胞及单核来源树突状细胞为主。MC38肿瘤中单核细胞与中性粒细胞占主导，同时伴有显著的T细胞浸润。B16-F10肿瘤则富含巨噬细胞，仅呈现中等程度的T细胞存在。综上所述，本研究系统阐述了不同异位肿瘤模型的免疫微环境特征，揭示了不同肿瘤实体间免疫细胞谱系的异质性。这些数据可为新型免疫疗法研究提供重要参考依据，因此本报告可作为临床前免疫治疗研究设计的实用工具。
Comparative Study of the Immune Microenvironment in Heterotopic Tumor Models
肿瘤(癌症)患者之家