Singapore Immunology Network, Singapore, Singapore.
Eur J Immunol. 2012 Jan;42(1):89-100. doi: 10.1002/eji.201141825. Epub 2011 Dec 12.
High 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.
高巨噬细胞浸润肿瘤通常与不良预后相关；然而，在结直肠癌、胃癌和皮肤癌中，观察到相反的情况，但这种现象背后的机制尚不清楚。在这里，我们试图了解结直肠癌中的肿瘤相关巨噬细胞 (TAMs) 如何发挥肿瘤抑制作用。我们发现，结直肠癌模型中的 TAMs 具有促炎作用，并抑制肿瘤细胞的增殖。TAMs 还产生趋化因子，吸引 T 细胞，刺激同种异体 T 细胞增殖，并激活与抗肿瘤免疫反应相关的 1 型 T 细胞。使用结直肠肿瘤组织，我们验证了体内的 TAMs 确实具有促炎作用。此外，肿瘤浸润 T 细胞的数量与 TAMs 的数量相关，这表明 TAMs 可以吸引 T 细胞；实际上，1 型 T 细胞存在于肿瘤组织中。患者临床数据表明，TAMs 在 T 细胞的帮助下发挥肿瘤抑制作用。因此，TAMs 在结直肠癌中的肿瘤抑制机制涉及抑制肿瘤细胞增殖以及产生促炎细胞因子、趋化因子和促进 1 型 T 细胞反应。这些新发现将有助于基于增强 TAMs 的肿瘤抑制特性来增强抗肿瘤免疫反应的未来癌症免疫疗法的发展。
