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The interweaving relationship between extracellular vesicles and T cells in cancer

Abu N, Rus Bakarurraini NAA

Cancer Lett, 2022 Apr 01;530:1-7.
PMID: 34906625 DOI: 10.1016/j.canlet.2021.12.007

The interdependency between cancer cells and immune cells is an important link in understanding cancer pathogenesis. T cells are important immune cells that are able to either impede or promote tumor growth. Extracellular vesicles or EVs are membrane-encapsulated vesicles that are released by both cancer and immune cells that can act as communicators. Studies have shown that tumor-derived EVs can interact with immune cells, particularly T cells. Vice versa, T cells-derived EVs have also been shown to possess immunomodulatory roles. Therefore, the purpose of this mini-review is to understand the role of tumor-derived EVs and T-cells derived EVs on cancer immunosuppression especially the interweaving role of different types of EVs and how it affects tumor immunity. We also discuss the role of EVs in different types of T cells namely CD8+, CD4+ Th17 and Treg cells. More importantly, we include the limitations and future directions involving this type of research. This will further elucidate our understanding of the important functions of these tiny mediators.
Fulltext The Landscape of Tumor-Specific Antigens in Colorectal Cancer

Rus Bakarurraini NAA, Ab Mutalib NS, Jamal R, Abu N

Vaccines (Basel), 2020 Jul 10;8(3).
PMID: 32664247 DOI: 10.3390/vaccines8030371

Over the last few decades, major efforts in cancer research and treatment have intensified. Apart from standard chemotherapy approaches, immunotherapy has gained substantial traction. Personalized immunotherapy has become an important tool for cancer therapy with the discovery of immune checkpoint inhibitors. Traditionally, tumor-associated antigens are used in immunotherapy-based treatments. Nevertheless, these antigens lack specificity and may have increased toxicity. With the advent of next-generation technologies, the identification of new tumor-specific antigens is becoming more important. In colorectal cancer, several tumor-specific antigens were identified and functionally validated. Multiple clinical trials from vaccine-based and adoptive cell therapy utilizing tumor-specific antigens have commenced. Herein, we will summarize the current landscape of tumor-specific antigens particularly in colorectal cancer.
Fulltext Extracellular Vesicles and DAMPs in Cancer: A Mini-Review

Abu N, Rus Bakarurraini NAA, Nasir SN

Front Immunol, 2021;12:740548.
PMID: 34721407 DOI: 10.3389/fimmu.2021.740548

Certain cancer therapy has been shown to induce immunogenic cell death in cancer cells and may promote tumor progression instead. The external stress or stimuli may induce cell death and contribute toward the secretion of pro inflammatory molecules. The release of damage-associated molecular patterns (DAMPs) upon induction of therapy or cell death has been shown to induce an inflammatory response. Nevertheless, the mechanism as to how the DAMPs are released and engage in such activity needs further in-depth investigation. Interestingly, some studies have shown that DAMPs can be released through extracellular vesicles (EVs) and can bind to receptors such as toll-like receptors (TCRs). Ample pre-clinical studies have shown that cancer-derived EVs are able to modulate immune responses within the tumor microenvironment. However, the information on the presence of such DAMPs within EVs is still elusive. Therefore, this mini-review attempts to summarize and appraise studies that have shown the presence of DAMPs within cancer-EVs and how it affects the downstream cellular process.
Fulltext Methylation Profile of Cancer Testis Antigens in Colorectal Cancer

Abu N, Rus Bakarurraini NAA, Nasir SN, Ishak M, Baharuddin R, Jamal R, et al.

Iran J Immunol, 2023 Mar 14;20(1):83-91.
PMID: 36932973 DOI: 10.22034/iji.2023.92600.2171

BACKGROUND: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.
OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.
METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.
RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.
CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.