癌症：免疫系統遠程攻擊腫瘤 Cancer: The immune system attacks tumors remotely

News Release 12-Mar-2020

Institut Pasteur

VIDEO: Video showing T lymphocytes (green) attacking a tumor (blue and orange). In vivo real-time experiments show how T lymphocytes act both locally and remotely within the tumor. view more 

Credit: © Ronan Thibaut and Philippe Bousso, Institut Pasteur / Inserm

How does the immune system act to limit tumor development? Using in vivo imaging tools, scientists from the Institut Pasteur and Inserm described the spatiotemporal activity of tumor-infiltrating T lymphocytes, both locally and remotely. Their research was published in the journal Nature Cancer on March 9, 2020.

Some cells in the immune system, like T lymphocytes, are capable of attacking cancer cells. Promising new therapies known as immunotherapies, recognized by the 2018 Nobel Prize in Medicine, attempt to boost the immune system’s response to cancer.

But how exactly do T lymphocytes act in tumors? T lymphocytes are killer cells that are capable of infiltrating a tumor and destroying cancer cells, one by one, through direct contact. This destruction of cancer cells is a highly local phenomenon that only occurs in the immediate vicinity of killer cells. But during these contacts, T lymphocytes also produce soluble molecules known as cytokines. Scientists from the Institut Pasteur and Inserm set out to understand the effect of one of these cytokines, known as interferon-gamma (IFN-γ), on the tumor microenvironment.

They used highly powerful imaging techniques to visualize, in real time and in vivo in mice, both the behavior of T lymphocytes and also the effect of IFN-γ within the tumor. The scientists observed that rather than acting locally, the cytokines spread rapidly within the tumor and affect cancer cells that may be distant from the T cells. “This remote action within the tumor is very interesting because it enables T lymphocytes to act on a large number of cancer cells, especially those that may have developed mechanisms to escape the immune system,” explains lead author Philippe Bousso, an Inserm researcher and Head of the Dynamics of Immune Responses Unit at the Institut Pasteur.

In their research, the scientists also demonstrated that the number of T lymphocytes that successfully infiltrate the tumor is correlated with the quantity of cytokine produced and determines the extent of tumor cell response. A study of melanoma patient cells supports this model of remote action by immune cells. Stimulating this collective response could therefore represent a key target for future immunotherapy approaches.

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癌症：免疫系統遠程攻擊腫瘤

免疫系統如何限制腫瘤的發展？巴斯德研究所（Institut Pasteur）和英瑟姆研究所（Inserm）的科學家利用體內成像工具描述了局部和遠處腫瘤浸潤性T淋巴細胞的時空活動。他們的研究於2020年3月9日發表在《自然癌症》雜誌上。

免疫系統中的某些細胞，例如T淋巴細胞，能夠攻擊癌細胞。獲得2018年諾貝爾醫學獎的有前途的新療法稱為免疫療法，旨在增強免疫系統對癌症的反應。

但是T淋巴細胞在腫瘤中的作用到底如何？ T淋巴細胞是殺傷細胞，能夠通過直接接觸一張一張地浸潤腫瘤並破壞癌細胞。癌細胞的這種破壞是高度局部的現象，僅發生在殺傷細胞的附近。但是在這些接觸過程中，T淋巴細胞也會產生稱為細胞因子的可溶性分子。巴斯德研究所（Institut Pasteur and Inserm）的科學家著手了解一種稱為乾擾素-γ（IFN-γ）的細胞因子對腫瘤微環境的影響。

他們使用功能強大的成像技術在小鼠中實時和體內觀察T淋巴細胞的行為以及腫瘤內IFN-γ的作用。科學家觀察到，細胞因子不是在局部起作用，而是在腫瘤內迅速擴散並影響可能與T細胞分離的癌細胞。 “腫瘤內的這種遠程作用非常有趣，因為它使T淋巴細胞能夠作用於大量癌細胞，尤其是那些可能具有逃避免疫系統機制的癌細胞，” Inserm研究人員兼負責人Philippe Bousso解釋說。研究所的免疫反應動力學研究室。

在他們的研究中，科學家還證明，成功滲入腫瘤的T淋巴細胞的數量與產生的細胞因子的數量有關，並決定了腫瘤細胞反應的程度。黑色素瘤患者細胞的研究支持了免疫細胞的這種遠程作用模型。因此，刺激這種集體反應可能代表未來免疫治療方法的關鍵目標。