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我们体内的真菌：真菌菌群在癌症中的新角色

2023年01月13日

来源：癌症研究UPDATE

以下内容原文发布于AACR官方博客《Cancer Research Catalyst》, 中文内容仅做参考，请点击文末“阅读原文”，阅览原文内容。

提到真菌，你会想到什么？蘑菇？脚气或癣？

你会想到癌症吗？

多年来，研究人员一直在探索细菌和病毒在癌症中的发挥的作用，研究表明细菌和病毒能够影响癌症的发展轨迹和治疗效果。而今，研究人员发现肿瘤及其周围环境中还存在各种真菌（包括所谓的真菌菌群），它们可以与细菌、细胞蛋白质和免疫细胞协同作用，从而影响癌症的进展和患者的预后。

2022年9月发表在杂志《Cell》上的两项“背靠背”癌症分析表明，真菌寄居在至少35种不同组织的肿瘤中，并且可能通过血流从肠道迁移到其他器官。癌症真菌菌群的组成具有组织特异性，真菌菌群和周围细菌之间的相互作用也具有组织特异性。

真菌与癌症共存的首个证据是2019年在胰腺癌中发现的，有人提出癌症相关的真菌可能会影响该癌症类型的发病和进展。在2022年美国癌症研究协会（AACR）年会上，以及在今年发表的一篇文章中，研究人员表示，在一部分胰腺癌中，真菌促进了一种叫做IL-33的免疫抑制蛋白的分泌，这可能使这些癌症避开免疫反应的抗肿瘤作用，从而进展到更晚期。有趣的是，KRAS蛋白的一种突变形式增加了IL-33的表达，这揭示了这种常见的突变体和真菌菌群在胰腺癌中的促肿瘤协作。

在这些观察结果的基础上，《Cell》杂志最新发表的几项研究也发现了真菌与癌症特征和临床结局之间的相关性。例如，假丝酵母属真菌的存在与胃癌中的炎症和免疫激活、头颈部和结肠癌中的促肿瘤基因表达变化、结肠癌的转移以及各种胃肠道癌症的生存率降低相关。研究人员发现，真菌和周围细菌菌群之间的相互作用也与临床结局相关。

了解更多内容，请阅读以下原文。

The Fungus Within Us: The Mycobiome’s Emerging Role in Cancer

By Neha J. Pancholi, PhD

What comes to mind when you think of a fungus? A mushroom? A case of athlete’s foot or ringworm?

How about cancer?

For years, researchers have explored the role of bacteria and viruses in cancer, demonstrating that these elements impact disease trajectories and treatment responses. Now, researchers have discovered that tumors and their surrounding milieu also house various fungal species—comprising what is known as the mycobiome—that could work in concert with bacteria, cellular proteins, and immune cells to influence cancer progression and patient prognosis.

According to two back-to-back cancer-wide analyses published in the September 2022 issue of Cell, fungi inhabit tumors arising in at least 35 different tissues, potentially relocating from the gut to other organs by way of the bloodstream. The compositions of cancer mycobiomes are tissue-specific, as are interactions formed between fungal communities and neighboring bacteria.

When the first evidence of fungi coexisting with cancer was reported in 2019 in pancreatic cancer, it was suggested that cancer-associated fungi might impact the onset and progression of this cancer type. At the AACR Annual Meeting 2022, and in an article published this year, researchers showed that in a subset of pancreatic cancers, fungi promoted the secretion of an immune-suppressing protein called IL-33, potentially enabling these cancers to circumvent the antitumor effects of the immune response and progress to more advanced stages. Interestingly, the expression of IL-33 was increased by a mutated form of the KRAS protein, thus revealing a tumor-promoting collaboration between this common mutant and the mycobiome in pancreatic cancer.

Building on these observations, the latest studies in Cell similarly identified correlations between fungi and cancer traits and outcomes. The presence of the Candida group of fungi, for example, was associated with inflammation and immune activation in stomach cancer, tumor-promoting gene expression changes in head-and-neck and colon cancers, metastasis in colon cancers, and reduced survival in various gastrointestinal cancers. Researchers found that interactions between fungi and surrounding bacterial communities correlated with outcomes, too.

Importantly, researchers could not determine whether the observed associations were causal. It is possible that the mycobiome directly or indirectly impacts tumor progression, but it is also feasible that fungal growth is a consequence of the environmental changes brought on by cancer development. Nonetheless, the recent findings could have important implications for cancer care.

A study from 2021 suggested that some fungi could negatively impact responses to radiation therapy by inhibiting antitumor immune functions, and studies from this year indicated that certain fungal species are associated with poor responses to immunotherapy in patients with melanoma. These findings raise the prospect of modulating the mycobiome to improve responses to cancer treatments.

Another idea is to utilize changes to the mycobiome as a biomarker of cancer onset or progression. Researchers showed that fungal DNA circulated in the blood, which might allow clinicians to screen for cancer by analyzing the mycobiome with just a simple blood draw.

While the relationship between the mycobiome and cancer is just beginning to be understood, it has become increasingly apparent that fungal species, like the bacteria and viruses studied before, could have a role in cancer, presenting new opportunities for treatment and disease monitoring.

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