Article
Oncology
Veronica Finisguerra, Tereza Dvorakova, Matteo Formenti, Pierre Van Meerbeeck, Lionel Mignion, Bernard Gallez, Benoit J. van den Eynde
Summary: Despite limitations in certain tumor types and patients, immunotherapies have achieved revolutionary success in cancer treatment. However, the efficacy of immunotherapies is dependent on the viability and functionality of tumor antigen-specific CD8 T cells within the immunosuppressive tumor microenvironment, where oxygen levels are often low. This study reveals that the antidiabetic drug metformin can improve CD8 T cell fitness in hypoxia, increasing their proliferation and cytokine production, and enhancing their infiltration and survival in hypoxic tumor areas. This presents a promising strategy to overcome resistance to immunotherapy in hypoxic and immunosuppressive tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Fumihiko Kinoshita, Tetsuzo Tagawa, Takaki Akamine, Kazuki Takada, Yuichi Yamada, Yuka Oku, Keisuke Kosai, Yuki Ono, Kensuke Tanaka, Sho Wakasu, Taro Oba, Atsushi Osoegawa, Mototsugu Shimokawa, Yoshinao Oda, Tomoaki Hoshino, Masaki Mori
Summary: High expression of IL-38 in tumor cells is significantly associated with reduced CD8(+)TILs and tumor progression, suggesting IL-38 could be a therapeutic target for lung cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Marco Pio La Manna, Diana Di Liberto, Marianna Lo Pizzo, Leila Mohammadnezhad, Mojtaba Shekarkar Azgomi, Vincenzo Salamone, Valeria Cancila, Davide Vacca, Costanza Dieli, Rosario Maugeri, Lara Brunasso, Domenico Gerardo Iacopino, Francesco Dieli, Nadia Caccamo
Summary: This study aimed to investigate the role of tissue-resident memory T cells (TRM) in the glioma tumor microenvironment. The findings showed an increased presence of CD8(+) TRM cells in gliomas, which were positively correlated with tumor-infiltrating lymphocytes (TILs) and associated with better survival outcomes. High expression of the gene coding for the integrin CD103 and high CD8(+) TILs abundance were associated with prolonged survival in glioma patients.
Article
Health Care Sciences & Services
Bogdan Marian Caraban, Elena Matei, Georgeta Camelia Cozaru, Mariana Aschie, Mariana Deacu, Manuela Enciu, Gabriela Izabela Baltatescu, Anca Chisoi, Nicolae Dobrin, Lucian Petcu, Emma Gheorghe, Laurentiu-Tony Hangan, Mihai Catalin Rosu, Cristian Ionut Orasanu, Antonela-Anca Nicolau
Summary: This study aimed to characterize the PD-L1 expression in melanomas and its association with T cell infiltrates. The results showed that most of the PD-L1 positive tumors had moderate scores of CD4+ and CD8+ TILs in tumoral melanoma cells. PD-L1 expression was associated with different degrees of lymphocytic infiltration and with Breslow tumor thickness. PD-L1 expression is a predictive biomarker for discriminating the presence or absence of malign tumoral melanoma cells and an independent predictor of good prognosis in melanoma patients.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Claire Y. Li, Hyeung Ju Park, Jinyeon Shin, Jung Eun Baik, Babak J. Mehrara, Raghu P. Kataru
Summary: This study suggests that lymphatic endothelial cells (LECs) can act as immunosuppressive cells in the tumor microenvironment (TME) in an MHC-II dependent manner. LECs in the TME increase MHC-II expression and co-inhibitory signals, suppressing the immune response. This finding highlights the importance of understanding the role of LECs in tumor immunity and opens up new avenues for therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Wei Shi, Mackenzie Fijardo, Jeff P. Bruce, Jie Su, Wei Xu, Rachel Bell, Pierre-Antoine Bissey, Angela B. Y. Hui, John Waldron, Trevor J. Pugh, Kenneth W. Yip, Fei-Fei Liu
Summary: This study reveals the prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in naso-pharyngeal cancer (NPC) and suggests the potential of utilizing CD8+ lymphocytes for immunotherapy.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Jose Manuel Casanova, Jani-Sofia Almeida, John David Reith, Luana Madalena Sousa, Ruben Fonseca, Paulo Freitas-Tavares, Manuel Santos-Rosa, Paulo Rodrigues-Santos
Summary: Osteosarcoma is a common high-grade primary bone tumor that mainly affects young adults. The presence of tumor-infiltrating CD4+ cells is protective for patients, while CD8+ cells have a significant impact on overall survival and progression-free survival. There is a strong association between tumor-infiltrating CD4+ cells and CD44s expression in tumor samples, highlighting the importance of considering TIL and tumor markers for improving OST treatment.
Article
Biochemistry & Molecular Biology
Satu Salmi, Kaisla Halinen, Anton Lin, Sanna Suikkanen, Otto Jokelainen, Eija Rahunen, Hanna Siiskonen, Sanna Pasonen-Seppanen
Summary: In melanoma, CD8+ and GrB+ lymphocytes were found to be more abundant in pT4 melanomas and lymph node metastases compared to primaries. A low GrB/CD8 ratio was associated with better recurrence-free survival in primary melanomas, suggesting that GrB+ lymphocytes may represent activated immunosuppressive lymphocytes.
Article
Oncology
Surbhi Bansil, Anthony Silva, Alana Taniguchi, Christina Wiedmer, Mayumi Fernandez, Ian Pagano, Koah Vierkoetter, Jeffrey Killeen, Jami Fukui
Summary: Tumor-infiltrating lymphocytes (TILs) have emerged as predictors of breast cancer treatment response and patient outcomes. This study provides preliminary data on the breast cancer tumor microenvironment for Asian and Native Hawaiian/Pacific Islander racial/ethnic groups, which are underrepresented in the literature.
Article
Oncology
Libin Zhang, Yanhui Chen, Han Wang, Zheyuan Xu, Yang Wang, Sixing Li, Jun Liu, Yun Chen, Hongli Luo, Lijia Wu, Ying Yang, Henghui Zhang, Hao Peng
Summary: CD8+PD-L1+ tumor-infiltrating lymphocytes in the tumor microenvironment of non-small cell lung cancer can serve as an indicator of a hot but immunosuppressive environment related to high tumor mutation burden. In immunotherapy, blocking the PD-1 pathway can help alleviate immunosuppression and lead to better treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Byung-Seok Kim, Da-Sol Kuen, Choong-Hyun Koh, Hyung-Don Kim, Seon Hee Chang, Sehui Kim, Yoon Kyung Jeon, Young-Jun Park, Garam Choi, Jiyeon Kim, Keon Wook Kang, Hye Young Kim, Suk-Jo Kang, Shin Hwang, Eui-Cheol Shin, Chang-Yuil Kang, Chen Dong, Yeonseok Chung
Summary: IL-17-producing cells promote terminal exhaustion of CD8(+) T cells and tumor progression in vivo, which can be reversed by blockade of IL-17 or ROR gamma t pathway. Human TCGA analyses reveal a strong positive correlation between type 17 and CD8(+) T cell exhaustion signature gene sets in multiple cancers, suggesting type 17 immunity as a promising target for cancer immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Chester Lai, George Coltart, Andrew Shapanis, Conor Healy, Ahmad Alabdulkareem, Sara Selvendran, Jeffrey Theaker, Matthew Sommerlad, Matthew Rose-Zerilli, Aymen Al-Shamkhani, Eugene Healy
Summary: The study identified a significant presence of CD8+CD103+ TRMs in cutaneous squamous cell carcinomas, with their expression in the tumor being associated with poorer clinical outcomes for patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Mahdi Abdoli Shadbad, Zahra Asadzadeh, Negar Hosseinkhani, Afshin Derakhshani, Nazila Alizadeh, Oronzo Brunetti, Nicola Silvestris, Behzad Baradaran
Summary: PD-L1 overexpression may be associated with poor prognosis in glioblastoma patients who have not undergone chemo-radiotherapy, while exposure to anti-cancer therapies such as chemo-radiotherapy can up-regulate inhibitory immune checkpoint molecules in tumor-infiltrating CD8(+) T-cells. Therefore, administering immune checkpoint inhibitors based on single-cell sequencing data from the tumor microenvironment cells can increase patients' response rates.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Hongyan Wu, Xinyi Tang, Hyo Jin Kim, Shahrzad Jalali, Joshua C. Pritchett, Jose C. Villasboas, Anne J. Novak, Zhi-Zhang Yang, Stephen M. Ansell
Summary: The study found that intratumoral CD8(+) cells in FL are skewed toward effector cell subsets, exhibiting increased capacity to produce cytokines/granules compared to memory cell subsets, but with inferior proliferative and viability capacities. The distribution of different CD8(+) cell subsets is associated with the prognosis of patients with FL.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Kosuke Imamura, Yusuke Tomita, Ryo Sato, Tokunori Ikeda, Shinji Iyama, Takayuki Jodai, Misako Takahashi, Akira Takaki, Kimitaka Akaike, Shohei Hamada, Shinya Sakata, Koichi Saruwatari, Sho Saeki, Koei Ikeda, Makoto Suzuki, Takuro Sakagami
Summary: This study found that the infiltration of drebrin-expressing T cells within the tumor cell nest in resectable squamous cell lung cancer patients is associated with short relapse-free survival and overall survival. The in vitro induced drebrin(+) T cells co-express multiple exhaustion-associated molecules. Single-cell RNA-sequencing analysis confirmed that exhausted tumor-infiltrating CD8(+) T cells specifically expressed drebrin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Ying Zhang, Hildegund C. J. Ertl
Article
Oncology
Ying Zhang, Hildegund C. J. Ertl
Article
Oncology
Zhuohan Zhang, Qiaofei Liu, Yongzhe Che, Xin Yuan, Lingyun Dai, Bin Zeng, Guohui Jiao, Yin Zhang, Xue Wu, Yinyan Yu, Yuan Zhang, Rongcun Yang
Article
Genetics & Heredity
S. Min, L. Li, M. Zhang, Y. Zhang, X. Liang, Y. Xie, Q. He, Y. Li, J. Sun, Q. Liu, X. Jiang, Y. Zhang, Y. Che, R. Yang
GENES AND IMMUNITY
(2012)
Article
Immunology
Ying Zhang, Hildegund C. J. Ertl
JOURNAL OF IMMUNOLOGY
(2014)
Article
Multidisciplinary Sciences
Zhibin Zhang, Ying Zhang, Shiyu Xia, Qing Kong, Shunying Li, Xing Liu, Caroline Junqueira, Karla F. Meza-Sosa, Temy Mo Yin Mok, James Ansara, Satyaki Sengupta, Yandan Yao, Hao Wu, Judy Lieberman
Article
Immunology
Jun Jacob Hu, Xing Liu, Shiyu Xia, Zhibin Zhang, Ying Zhang, Jingxia Zhao, Jianbin Ruan, Xuemei Luo, Xiwen Lou, Yang Bai, Junhong Wang, L. Robert Hollingsworth, Venkat Giri Magupalli, Li Zhao, Hongbo R. Luo, Justin Kim, Judy Lieberman, Hao Wu
Article
Multidisciplinary Sciences
Ying Zhang, Xuemei Xie, Pourya Naderi Yeganeh, Dian-Jang Lee, David Valle-Garcia, Karla F. Meza-Sosa, Caroline Junqueira, Jiayu Su, Hongbo R. Luo, Winston Hide, Judy Lieberman
Summary: New cancer immunotherapy strategies using EpCAM aptamer-linked small-interfering RNA chimeras (AsiCs) were effective in selectively knocking down genes in EpCAM(+) tumors to enhance immune recognition. Four of the six AsiC (Upf2, Parp1, Cd47, and Mcl1) were able to inhibit tumor growth and improve tumor-infiltrating immune cell functions. AsiC mixtures showed better efficacy than individual AsiC and could synergize with anti-PD-1 checkpoint inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Karla F. Meza-Sosa, Rui Miao, Francisco Navarro, Zhibin Zhang, Ying Zhang, Jun Jacob Hu, Corrine Corrina R. Hartford, Xiao Ling Li, Gustavo Pedraza-Alva, Leonor Perez-Martinez, Ashish Lal, Hao Wu, Judy Lieberman
Summary: The p53-induced lncRNA SPARCLE enhances p53-mediated apoptosis by promoting PARP-1 cleavage, leading to interference with DNA damage repair.
Article
Multidisciplinary Sciences
Setu M. Vora, Pietro Fontana, Tianyang Mao, Valerie Leger, Ying Zhang, Tian-Min Fu, Judy Lieberman, Lee Gehrke, Ming Shi, Longfei Wang, Akiko Iwasaki, Hao Wu
Summary: A study has found that SARS-CoV-2 utilizes its nonstructural protein 1 (Nsp1) to suppress host protein synthesis, but targeting the SL1 region of the SARS-CoV-2 5' untranslated region (5' UTR) can evade Nsp1-mediated translational suppression and hinder viral replication. The findings provide a conservative therapeutic target for COVID-19.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Correction
Multidisciplinary Sciences
Sumit Sen Santara, Dian-Jang Lee, Angela Crespo, Jun Jacob Hu, Caitlin Walker, Xiyu Ma, Ying Zhang, Sourav Chowdhury, Karla F. Meza-Sosa, Mercedes Lewandrowski, Haiwei Zhang, Marjorie Rowe, Arthur McClelland, Hao Wu, Caroline Junqueira, Judy Lieberman
Article
Multidisciplinary Sciences
Sumit Sen Santara, Dian-Jang Lee, Angela Crespo, Jun Jacob Hu, Caitlin Walker, Xiyu Ma, Ying Zhang, Sourav Chowdhury, Karla F. Meza-Sosa, Mercedes Lewandrowski, Haiwei Zhang, Marjorie Rowe, Arthur McClelland, Hao Wu, Caroline Junqueira, Judy Lieberman
Summary: Natural killer (NK) cells can recognize externalized calreticulin (ecto-CRT) as an endogenous ligand for the activating receptor NKp46. Recognition of ecto-CRT by NKp46 triggers NK cell signaling and leads to the elimination of ER-stressed cells. This recognition mechanism plays a crucial role in immune surveillance and cancer prevention.
Article
Oncology
Ying Zhang, Raj Kurupati, Ling Liu, Xiang Yang Zhou, Gao Zhang, Abeer Hudaihed, Flavia Filisio, Wynetta Giles-Davis, Xiaowei Xu, Giorgos C. Karakousis, Lynn M. Schuchter, Wei Xu, Ravi Amaravadi, Min Xiao, Norah Sadek, Clemens Krepler, Meenhard Herlyn, Gordon J. Freeman, Joshua D. Rabinowitz, Hildegund C. J. Ertl