Colt A Egelston, Weihua Guo, Diana L Simons, Jian Ye, Christian Avalos, Shawn T Solomon, Mary Nwangwu, Michael S Nelson, Jiayi Tan, Eliza R Bacon, Kena Ihle, Daniel Schmolze, Lusine Tumyan, James R Waisman, Peter P Lee
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引用次数: 0
Abstract
Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer to metastasize and to respond to therapy. Previous studies suggested that the metastatic TME is immune suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessment of the immune TME in the context of multi-organ metastases difficult. We utilized a rapid postmortem tissue collection protocol to assess immune composition in numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases were found to have comparable immune cell densities and composition to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues were significantly different between organ types, with lung immune infiltration consistently greater than liver. These immune profiling results were consistent between both flow cytometry and multiplex immunofluorescence-based spatial analysis. Furthermore, we found granulocytes were a predominant tumor-infiltrating immune cell in both lung and liver metastases and these granulocytes made up the majority of PD-L1-expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with lung having increased expression of PD-L1+ antigen-presenting cells and liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together these results demonstrate that immune contexture of metastases is dictated by organ type, and that immunotherapy strategies may benefit from unique tailoring to tissue-specific features of the immune TME.
期刊介绍:
Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes.
Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.