Immune landscape of colorectal cancer lung metastasis.

Abstract

e15542 Background: Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death worldwide. What makes CRC treatment a challenge is synchronous or metachronous recurrence at distant organs; metastasis. Approximately half of CRC patients develop metastases in the course of the disease and the most prevalent metastatic site is liver, followed by lung and peritoneum. A 5-year survival rate metastatic CRC is much poorer than that of patients with regional and localized CRC. Methods: From 2019 to 2020, 9 metastatic CRC patients who had recurrence to lung oligo-metastases were enrolled. These patients were eligible for lung metastatectomy of curative intent. The surgically resected lung metastases were collected and whole exome sequencing/RNA sequencing,10x chromium single cell RNA sequencing analysis were performed. The purpose of this study was to uncover distinctive tumor microrenvironment (TME) of the lung metastases from CRC, we compared these results with those from public available primary CRC data. Results: We successfully analyzed all 9 metastatic lung samples. Compared to primary CRC, we found that lung metastasis had more immune-suppressive TMEs, represented by downregulation of TCR signaling, innate/adaptive immune system and antigen presentation. In addition, there were higher expression levels of immune checkpoint molecules, such as PD-1, LAG-3 and TIGIT in metastatic lung samples when compared to primary colon cancer public database. Macrophage polarization of lung metastases toward alternatively activated M2 subset, rather than classically activated M1 subset, resulting in low M1/M2 ratio, was also thought to attribute to immune suppressive environments of the lung metastases and successful colonization of primary tumors. Conclusions: This study identified different TMEs of lung metastasis specimens from primary CRCs. Our study underscores the importance of the tumor microenvironment and the anatomic location of the tumor cells for optimized immunotherapeutic strategies.