Tan Lih Yin, Martini Carmela, Fridlender Zvi G, Bonder Claudine S, Brown Michael P, Ebert Lisa M
Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
Clin Transl Immunology. 2017 Mar 17;6(3):e134. doi: 10.1038/cti.2017.7. eCollection 2017 Mar.
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8 cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis. Access and infiltration of circulating leukocytes into the tumour is governed by adhesion molecules and chemokines expressed by the endothelial cells of the vasculature. This review focuses on the adhesion molecules and chemokines which control the homing of CD8 cytotoxic T-cells, monocytes and neutrophils to peripheral tissues, including tumours. We discuss the role of these leukocyte subsets in regulating melanoma growth, and detail the mechanisms used by tumours to selectively recruit or exclude these leukocytes for their own advantage. In doing so, we bring to light an underappreciated component of tumour biology which should be considered in combination with current treatments to selectively alter the leukocyte composition of tumours and ultimately enhance treatment outcome.
转移性黑色素瘤对全球许多人来说仍然是一种致命疾病，即使在引入了如BRAF抑制剂等靶向治疗以及如CTLA-4和PD-1抑制剂等免疫检查点阻断疗法之后。随着我们对这种疾病理解的进步，以及从患者研究中收集到的数据不断增加，宿主免疫反应对癌症进展和治疗反应的重要性正变得清晰。更具体地说，肿瘤内CD8细胞毒性T细胞的存在与较好的预后相关，而肿瘤中单核细胞/巨噬细胞和中性粒细胞的积累通常与较差的预后相关。循环白细胞进入肿瘤的过程受血管内皮细胞表达的黏附分子和趋化因子的调控。本综述聚焦于控制CD8细胞毒性T细胞、单核细胞和中性粒细胞归巢至外周组织（包括肿瘤）的黏附分子和趋化因子。我们讨论了这些白细胞亚群在调节黑色素瘤生长中的作用，并详细阐述了肿瘤为自身利益选择性招募或排除这些白细胞所采用的机制。通过这样做，我们揭示了肿瘤生物学中一个未得到充分重视的组成部分，应将其与当前治疗方法结合考虑，以选择性地改变肿瘤中的白细胞组成，最终提高治疗效果。
