• Title/Summary/Keyword: Cancer, Immunotherapy

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Are So-Called Cancer-Testis Genes Expressed Only in Testis?

  • Ghafouri-Fard, Soudeh;Rezazadeh, Fatemeh;Zare-Abdollahi, Davood;Omrani, Mir Davood;Movafagh, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7703-7705
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    • 2014
  • Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

  • In-Ho Kim
    • Journal of Gastric Cancer
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    • v.24 no.1
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    • pp.29-56
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    • 2024
  • In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

Unveiling the Gastrointestinal Microbiome Symphony: Insights Into Post-Gastric Cancer Treatment Microbial Patterns and Potential Therapeutic Avenues

  • Chan Hyuk Park
    • Journal of Gastric Cancer
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    • v.24 no.1
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    • pp.89-98
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    • 2024
  • This review delved into the intricate relationship between the gastrointestinal microbiome and gastric cancer, particularly focusing on post-treatment alterations, notably following gastrectomy, and the effects of anticancer therapies. Following gastrectomy, analysis of fecal samples revealed an increased presence of oral cavity aerotolerant and bile acid-transforming bacteria in the intestine. Similar changes were observed in the gastric microbiome, highlighting significant alterations in taxon abundance and emphasizing the reciprocal interaction between the oral and gastric microbiomes. In contrast, the impact of chemotherapy and immunotherapy on the gut microbiome was subtle, although discernible differences were noted between treatment responders and non-responders. Certain bacterial taxa showed promise as potential prognostic markers. Notably, probiotics emerged as a promising approach for postgastrectomy recovery, displaying the capacity to alleviate inflammation, bolster immune responses, and maintain a healthy gut microbiome. Several strains, including Bifidobacterium, Lactobacillus, and Clostridium butyricum, exhibited favorable outcomes in postoperative patients, suggesting their potential roles in comprehensive patient care. In conclusion, understanding the intricate interplay between the gastrointestinal microbiome and gastric cancer treatment offers prospects for predicting responses and enhancing postoperative recovery. Probiotics, with their positive impact on inflammation and immunity, have emerged as potential adjuncts in patient care. Continued research is imperative to fully harness the potential of microbiome-based interventions in the management of gastric cancer.

Anticancer Effect of Activated Natural Killer Cells on Human Colorectal Tumor (결장암에 대한 활성 자연살해세포의 항암효능)

  • Sung, Hye-Ran;Kim, Jee-Youn;Park, Min-Gyeong;Kim, Il-Hoi;Lee, Dong-Wook;Han, Sang-Bae;Lee, Chong-Kil;Song, Suk-Gil
    • YAKHAK HOEJI
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    • v.54 no.3
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    • pp.192-199
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    • 2010
  • Colorectal cancer is one of the most common alimentary malignancies. In this study, the antitumor activity of activated human natural killer (NK) cells against human colorectal cancer was evaluated in vivo. Human NK cells are the key contributors of innate immune response and the effective functions of these cells are enhanced by cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured with interleukin-2 (IL-2)-containing medium for 14 days and resulted in enriched NK cell population. The resulting populations of the cells comprised 7% $CD3^+CD4^+$ cells, 25% $CD3^+CD8^+$ cells, 13% $CD3^-CD8^+$ cells, 4% $CD3^+$CD16/$CD56^+$ cells, 39% $CD3^+$CD16/$CD56^-$ cells, and 52% $CD3^-$CD16/$CD56^+$ cells. Tumor necrosis factor alpha (TNF-$\alpha$), interferon gamma (IFN-$\gamma$), IL-2, IL-4, and IL-5 transcripts of the activated NK cells were confirmed by RT-PCR. In addition, activated NK cells at doses of 2.5, 5 and 10 million cells per mouse inhibited 10%, 34% and 47% of SW620-induced tumor growth in nude mouse xenograft assays, respectively. This study suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for colorectal cancer patients.

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

  • Kim, Nayoung;Lee, Dong-Hee;Choi, Woo Seon;Yi, Eunbi;Kim, HyoJeong;Kim, Jung Min;Jin, Hyung-Seung;Kim, Hun Sik
    • BMB Reports
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    • v.54 no.1
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    • pp.44-58
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    • 2021
  • Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

The therapeutic potential of immune cell-derived exosomes as an alternative to adoptive cell transfer

  • Hong, Yeonsun;Kim, In-San
    • BMB Reports
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    • v.55 no.1
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    • pp.39-47
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    • 2022
  • Adoptive cell transfer (ACT), a form of cell-based immunotherapy that eliminates cancer by restoring and strengthening the body's immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident or peripheral blood-modified immune cells into cancer patients to mediate anti-tumor response. Although these immune cells control and eradicate cancer via enhanced cytotoxicity against specific tumor antigens, several side effects have been frequently reported in clinical trials. Recently, exosomes, potential cell-free therapeutics, have emerged as an alternative to cell-based immunotherapies, due to their higher stability under same storage condition, lower risk of GvHD and CRS, and higher resistance to immunosuppressive tumor microenvironment. Exosomes, which are nano-sized lipid vesicles, are secreted by living cells, including immune cells. Exosomes contain proteins, lipids, and nucleic acids, and the functional role of each exosome is determined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cells and NK cells exert anti-tumor effects via proteins such as granzyme B and FasL. In this mini-review, we describe the current understanding of the ACT and immune cell-derived exosomes and discuss the limitations of ACT and the opportunities for immune cell-derived exosomes as immune therapies.