Hae-Ock Lee, Yourae Hong, Hakki Emre Etlioglu, Yong Beom Cho, Valentina Pomella, Ben Van den Bosch, Jasper Vanhecke, Sara Verbandt, Hyekyung Hong, Jae-Woong Min, Nayoung Kim, Hye Hyeon Eum, Junbin Qian, Bram Boeckx, Diether Lambrechts, Petros Tsantoulis, Gert De Hertogh, Woosung Chung, Taeseob Lee, Minae An, Hyun-Tae Shin, Je-Gun Joung, Min-Hyeok Jung, Gunhwan Ko, Pratyaksha Wirapati, Seok Hyung Kim, Hee Cheol Kim, Seong Hyeon Yun, Iain Bee Huat Tan, Bobby Ranjan, Woo Yong Lee, Tae-You Kim, Jung Kyoon Choi, Young-Joon Kim, Shyam Prabhakar, Sabine Tejpar, Woong-Yang Park
Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.