Tissue-specific recruitment of regulatory T cells in colorectal cancer and liver metastases

结直肠癌是英国第三大常见癌症，仅次于乳腺癌和肺癌。结直肠癌有三分之一的患者是致命的，这是由于在诊断时疾病扩散到其他器官或在以后疾病复发。含有大量淋巴细胞（一种白色血细胞）的结直肠癌患者比含有较少淋巴细胞的癌症患者在提高生存率方面预后更好。有人提出，这些淋巴细胞代表了人体天然免疫系统对癌症的有利反应。一组被称为调节性T细胞的特定淋巴细胞可以抑制身体的免疫反应，这些细胞也在结直肠癌中大量存在。肿瘤中的调节性T细胞可以抑制其他淋巴细胞攻击肿瘤。因此，结肠直肠癌理想地含有攻击癌症的淋巴细胞和最小数量的抑制性调节性T细胞。已知淋巴细胞，包括调节性T细胞，通过称为趋化因子和粘附分子的不同分子的网络被募集到体内的不同组织。调节性T细胞也可以由其他淋巴细胞形成，这一过程称为诱导。我们建议将研究重点放在确定哪些归巢分子存在于调节性T细胞上，以及哪些分子在将这些抑制性细胞运输到结直肠癌中时很重要。目的是能够使用归巢分子的抑制剂阻断调节性T细胞募集到肿瘤中，同时允许效应（非抑制性）淋巴细胞不减弱地进入癌症。这提供了一种支持人体天然抗肿瘤免疫反应的方法，并将成为治疗结直肠癌的新方法。我们还将鉴定结直肠癌中存在的其他免疫细胞，这些细胞可能负责在癌组织中诱导调节性T细胞。这项研究将在伯明翰大学和伊丽莎白女王医院进行，并将使用从结直肠癌手术患者中获得的组织。将从组织中提取淋巴细胞，并分析存在的归巢分子。将进一步详细研究已鉴定的重要分子，包括如果使用药物阻断归巢分子，淋巴细胞的反应如何不同。

Colorectal cancer is the third most common cancer in the United Kingdom after breast and lung cancer. Colorectal cancer is deadly in one-third of patients due to either spread of the disease to other organs at the time of diagnosis or recurrence of the disease later on. Patients with colorectal cancers containing a large number of lymphocytes (a type of white blood cell) have a better prognosis in terms of improved survival than patients with cancers containing fewer lymphocytes. It is proposed that these lymphocytes represent a favourable response to the cancer by the body's natural immune system. A specific group of lymphocytes known as regulatory T cells can suppress the body's immune response and these are also found in abundance in colorectal cancers. Regulatory T cells in tumours can inhibit other lymphocytes from attacking the tumour. Colorectal cancers would therefore ideally contain lymphocytes attacking the cancer and a minimal number of suppressive regulatory T cells. It is known that lymphocytes, including regulatory T cells, are recruited to different tissues in the body via a network of different molecules known as chemokines and adhesion molecules. Regulatory T cells can also be formed from other lymphocytes, a process known as induction.We propose to focus our research on identifying which homing molecules are present on regulatory T cells and which are important in trafficking these suppressive cells into colorectal cancers. The intention is to be able to block recruitment of regulatory T cells into tumours using inhibitors of homing molecules while at the same time allowing effector (non-suppressive) lymphocytes into the cancer unabated. This provides a means to support the body's natural anti-tumour immune response and would be a new means of treating colorectal cancer. We will also identify other immune cells present in colorectal cancer which may be responsible for inducing regulatory T cells within the cancer tissue.The research will be conducted at the University of Birmingham and Queen Elizabeth hospital and will use tissue obtained from patients operated on for colorectal cancer. Lymphocytes will be extracted from the tissue and the homing molecules present will be analysed. Identified important molecules will be studied in further detail including how the lymphocytes respond differently if the homing molecules are blocked by using drugs.