CD47 is a tumor cell-derived exosomal signature and regulates tumor immune microenvironment and immunotherapy responses

Background: The pathogenesis of ovarian cancer (OvCa) involves a complex interplay of genetic, environmental, and hormonal factors. With the in-depth exploration of tumor ecosystem, exosomes can mediate the immunological status of tumor microenvironment (TME). Therefore, we aimed to recognize the tumor-derived exosomes (TEXs) which can distinguish the immune-hot and cold tumors and reflect the immunotherapeutic responses. Methods: A large set of transcriptomic and single-cell RNA-sequencing (scRNA-seq) datasets were downloaded and used to analyze the expression pattern of CD47 and its immuno-correlations in OvCa and multiple epithelial cell carcinomas such as breast cancers. In addition, a pan-gynecological cancer cohort was used to validate the correlation between CD47 and the inflamed TME. Results: In the current study, we found that CD47 was a TEX signature and had no transcriptional differences among patients with different clinicopathological features. Moreover, CD47 expression was positively correlated with the activation of immunological signaling pathways and enrichment of immune cell subpopulations in OvCa. Furthermore, in breast cancer and gynecological cancers, CD47, specially expressed in tumor cells, also showed favorable ability to distinguish the immune-hot and cold carcinomas. Moreover, in immunotherapy cohorts of breast cancer and other epithelial cell carcinomas, patients with CD47-high phenotype were more sensitive to immunotherapy and tended to achieve remission after treatment. Results from the TMA showed that CD47 was upregulated in tumor tissues and positively correlated with CD8 level. Conclusion: In conclusion, CD47 is associated with an inflammatory TME, immune-hot tumors, and sensitivity of immunotherapy, highlighting the values of CD47 in identifying immunological traits and an immunotherapeutic response.