دانلود مقاله نقش متابولیک چندجانبه عفونت ها در ریز محیط تومور
اختصارات
مقدمه
باکتری هایی که ریزمحیط تومور را تغییر می دهند و باعث رشد و متاستاز تومور می شوند
باکتری های مهندسی شده در درمان سرطان
ویروس های انکولیتیک و انکوژنیک
رویکردهای ویروس درمانی
ویروس آنفلوانزا A به عنوان یک عامل ویروسی در درمان سرطان
پروفایل متابولیک ریزمحیط تومور در طول عفونت ویروس آنفولانزای A
جهت های آینده
نتیجه گیری
بیانیه مشارکت نویسنده CRediT
اعلامیه منافع رقابتی
قدردانی ها
در دسترس بودن داده ها
مراجع و خواندن توصیه شده
Abbreviations
Introduction
Bacteria altering the tumor microenvironment, promoting tumor growth and metastasis
Engineered bacteria in cancer therapy
Oncolytic and oncogenic viruses
Approaches in virotherapy
Influenza A virus as a viral agent in cancer therapy
Metabolic profiling of the tumor microenvironment during influenza A virus infection
Future directions
Conclusion
CRediT authorship contribution statement
Declaration of Competing Interest
Acknowledgements
Data Availability
References and recommended reading
چکیده
تاثیر باکتری ها و ویروس ها بر رشد تومور مدت هاست که شناخته شده است. در دهه های اخیر، علاقه به نقش میکروارگانیسم ها در ریزمحیط تومور (TME) گسترش یافته است. عفونت ها برنامه ریزی مجدد متابولیک را تحریک می کنند و بر پاسخ های ایمنی در TME تأثیر می گذارند که ممکن است از تکثیر و متاستاز حمایت کند یا رشد تومور را محدود کند. توانایی طبیعی برای آلوده کردن سلول ها و تغییر TME نیز برای تشخیص و درمان سرطان استفاده می شود. در این بررسی، اکتشافات اخیر در مورد مکانیسم‌های باکتری‌ها و ویروس‌های موثر بر TME و همچنین استراتژی‌های درمان سرطان با تمرکز بر تغییرات متابولیک را مورد بحث قرار می‌دهیم. عفونت با باکتری‌ها و ویروس‌های مهندسی‌شده، رویکردهای درمانی امیدوارکننده‌ای را برای توسعه درمان‌های جدید و مؤثرتر برای محدود کردن رشد تومور نشان می‌دهد.
Introduction
Tumor microenvironment (TME) is a complex network of cancer cells and various other cellular and noncellular components. Microorganisms such as bacteria, viruses, fungi, phages, and protozoa naturally occur in the TME, modulating the metabolic composition and promoting or inhibiting tumorigenesis. In the last decades, a growing interest has emerged in microorganisms in the TME and their potential applications for cancer therapy 1, 2.
Bacterial and viral infections have been long associated with cancer development and have been used in cancer therapy decades ago. Bacteria have various effects on cancer cells through different modes of action, for instance, depending on the strain, tissue, and environment 1, 2. Viruses also naturally occur in the TME, and some strains promote cancer growth, such as the human papillomavirus (HPV) [3], while others have oncolytic activity, such as the influenza A virus (IAV) [4]. The different mechanisms through which bacteria and viruses affect tumor proliferation and metastasis include altering immune responses 5, 6, 7•, secreting cytotoxic molecules such as formate or colibactine 8••, 9, and alterations of metabolic and signaling pathways 8••, 10. The natural abilities of microorganisms to colonize and alter the TME can also be used for cancer detection and therapy with the help of engineered bacteria and viruses 2, 11, 12. However, the metabolic interactions among viruses, bacteria, cancer cells, and TME are not well understood. Metabolites function as signaling molecules, and we are just beginning to understand the functional role of small molecules within the TME 13, 14, 15. For instance, the immunometabolite itaconate has antimicrobial properties but may also affect tumor progression by altering cancer cell metabolism or the composition of the TME 16, 17•, 18, 19. Thus, further research is needed to identify the key players within the TME that affect immune responses and tumor progression.
Approaches in virotherapy
Virotherapy aims to transform the ‘cold’ immunosuppressive TME, characterized by high levels of TAMs, T-regulatory cells (Tregs), MDSCs, and activated M2-like macrophages, into a ‘hot’ immunoreactive TME (Figure 3). This transformation involves the recruitment of, for instance, NKs, DCs, and M1-like macrophages (Figure 3). OV administration targets different approaches in cancer therapies, such as making the virus dependent on specific genes within the cancer host cell to enable selective replication in malignant cells, followed by direct lysis. Furthermore, it is applied to deliver specific antibodies to inhibit tumor growth [45]. For instance, the recombinant human type-5 adenovirus (Ad5) selectively replicates in tumor cells with p53-defective influencing cancer cell growth [46]. OVs may also indirectly affect the TME and tumor growth by inducing the release of cytokines, such as interferon (IFN), damage-associated molecular patterns (DAMPs), high mobility group box 1 protein (HMGB1), or pathogen-associated molecular patterns (PAMPs) 41, 47, leading to further recruiting and activation of the innate and adaptive immune system, including DCs (Figure 3). DCs play an elementary role in connecting both immune systems and are infrequently present in the cold TME. These findings highlight various targets that can be used to modulate the immune response in the TME through OVs, aiming to constrain tumor growth and increase patient outcomes.
Conclusion
Bacterial and viral infections play a vital role in altering the composition of the TME, thus influencing its potential as pro- or anti-tumorigenic. Many bacteria and viruses influence TME, for instance, by secreting signal molecules, altering specific immune responses, causing DNA damage, or inducing metabolic rewiring. While promising approaches utilizing bacteria and viruses for cancer detection and therapy exist, how infections influence metabolism to promote either pro- or antitumor properties is still not well understood. Engineered bacteria and viruses could be optimized to work effectively against cancer with potentially less off-target effects compared with conventional therapies. For example, altering levels of cytokines or metabolites such as itaconate or arginine in the TME may promote an anticancer immune response, either alone or in combination with existing treatments. Expanding our current knowledge of the complex interaction of microorganisms and cancer cells will provide us with effective ways to develop new treatment strategies.