Macrophages in human colorectal cancer are pro‐inflammatory and prime T cells towards an anti‐tumour type‐1 inflammatory response

• DOI: 10.1002/eji.201141825
• Publication Date: 2011-10-18T16:38:21Z
• Authors: Siew‐Min Ong; Yann‐Chong Tan; Ottavio Beretta; Dongsheng Jiang; Wei‐Hseun Yeap; June J. Y. Tai; Wing‐Cheong Wong; Henry Yang; Herbert Schwarz; Kiat‐Hon Lim; Poh‐Koon Koh; Khoon‐Lin Ling; Siew‐Cheng Wong
• Keywords: 0301 basic medicine; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Macrophages; Th1 Cells; Real-Time Polymerase Chain Reaction; Immunohistochemistry; Coculture Techniques; 3. Good health; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Cytokines; Humans; RNA; Colorectal Neoplasms; HT29 Cells

AbstractHigh macrophage infiltration into tumours often correlates with poor prognoses; in colorectal, stomach and skin cancers, however, the opposite is observed but the mechanisms behind this phenomenon remain unclear. Here, we sought to understand how tumour‐associated macrophages (TAMs) in colorectal cancer execute tumour‐suppressive roles. We found that TAMs in a colorectal cancer model were pro‐inflammatory and inhibited the proliferation of tumour cells. TAMs also produced chemokines that attract T cells, stimulated proliferation of allogeneic T cells and activated type‐1 T cells associated with anti‐tumour immune responses. Using colorectal tumour tissues, we verified that TAMs in vivo were indeed pro‐inflammatory. Furthermore, the number of tumour‐infiltrating T cells correlated with the number of TAMs, suggesting that TAMs could attract T cells; and indeed, type‐1 T cells were present in the tumour tissues. Patient clinical data suggested that TAMs exerted tumour‐suppressive effects with the help of T cells. Hence, the tumour‐suppressive mechanisms of TAMs in colorectal cancer involve the inhibition of tumour cell proliferation alongside the production of pro‐inflammatory cytokines, chemokines and promoting type‐1 T‐cell responses. These new findings would contribute to the development of future cancer immunotherapies based on enhancing the tumour‐suppressive properties of TAMs to boost anti‐tumour immune responses.