Article
Biochemical Research Methods
Peng Zhang, Mingyue Liu, Ya Cui, Pan Zheng, Yang Liu
Summary: This study found that MSI-H and non-MSI-H samples exhibited clinical response and immune phenotypic differences in different cancer types. However, regardless of cancer types, the abundance of tumor-infiltrating immune cells was more strongly associated with clinical outcomes.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Biology
Carmelo Laface, Riccardo Memeo, Felicia Maria Maselli, Anna Natalizia Santoro, Maria Laura Iaia, Francesca Ambrogio, Marigia Laterza, Gerardo Cazzato, Chiara Guarini, Pierluigi De Santis, Martina Perrone, Palma Fedele
Summary: Immunotherapy is not effective for pancreatic cancer due to the unique features of the tumor microenvironment and the lack of useful biomarkers for evaluation.
Article
Oncology
Kelly Boelaars, Laura Goossens-Kruijssen, Di Wang, Charlotte M. de Winde, Ernesto Rodriguez, Dimitri Lindijer, Babet Springer, Irene van der Haar avila, Aram de Haas, Laetitia Wehry, Louis Boon, Reina E. Mebius, Nadine van Montfoort, Manfred Wuhrer, Joke M. M. den Haan, Sandra J. van Vliet, Yvette van Kooyk
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer, and immunotherapy has been unsuccessful in its treatment. This study shows that tumor-derived sialic acids play a critical role in shaping the immune landscape of PDAC. The absence of sialic acids allows for better infiltration of T cells into the tumor, resulting in improved response to immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Daniel R. Principe, Murray Korc, Suneel D. Kamath, Hidayatullah G. Munshi, Ajay Rana
Summary: Immunotherapy has revolutionized cancer treatment in the past decade, but has faced exceptional challenges in pancreatic ductal adenocarcinoma. Despite many different immunotherapies being explored in clinical trials, few have shown significant therapeutic efficacy.
Article
Oncology
Eva Karamitopoulou, Andreas Andreou, Anna Silvia Wenning, Beat Gloor, Aurel Perren
Summary: This study links tumor mutational burden (TMB) levels with immune pathway activation and intratumoral immune responses in pancreatic adenocarcinoma (PDAC). The results show that TMB-high cases frequently belong to specific PDAC subsets with prolonged survival and display strong anti-tumor immune responses.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Davide Melisi, Do-Youn Oh, Antoine Hollebecque, Emiliano Calvo, Anna Varghese, Erkut Borazanci, Teresa Macarulla, Valeria Merz, Camilla Zecchetto, Yumin Zhao, Ivelina Gueorguieva, Michael Man, Leena Gandhi, Shawn T. Estrem, Karim A. Benhadji, Mark C. Lanasa, Emin Avsar, Susan C. Guba, Rocio Garcia-Carbonero
Summary: The study assessed the safety, efficacy, and pharmacokinetics of the combination therapy of galunisertib and durvalumab in patients with recurrent/refractory metastatic pancreatic cancer. The results showed tolerability of the combination therapy, with limited clinical activity observed. Further studies in patients in earlier lines of treatment or with predictive biomarkers of TGF beta inhibition may be more suitable.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Medicine, Research & Experimental
Hongquan Qin, Jiali Chen, Katia Bouchekioua-Bouzaghou, Ya-Ming Meng, Jordi Bach Griera, Xue Jiang, Xiangzhan Kong, Minghui Wang, Qiuping Xu, Ping-Pui Wong
Summary: The study found that MAGEA regulates tumor-stromal crosstalk in PDAC, with high expression correlating with poor chemotherapeutic response and prognosis in multiple cancers. The mechanism includes inhibition of gemcitabine-induced cancer cell apoptosis and activation of GDF15 secretion to enhance gemcitabine resistance. Targeting MAGEA-mediated paracrine regulation of chemoresistance by immunotherapy could be a promising strategy for pancreatic cancer treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Chiara Musiu, Simone Caligola, Rosalinda Trovato, Alessandra Fiore, Cristina Frusteri, Cristina Anselmi, Ornella Poffe, Tiziana Cestari, Stefania Cane, Silvia Sartoris, Rosalba Giugno, Giulia Del Rosario, Barbara Zappacosta, Francesco Del Pizzo, Matteo Fassan, Erica Dugnani, Lorenzo Piemonti, Emanuela Bottani, Ilaria Decimo, Salvatore Paiella, Roberto Salvia, Rita Teresa Lawlor, Vincenzo Corbo, Youngkyu Park, David A. Tuveson, Claudio Bassi, Aldo Scarpa, Manuela Iezzi, Stefano Ugel, Vincenzo Bronte
Summary: PDAC tumors exhibit strong immunosuppressive characteristics that limit the success of immunotherapy. Research shows that reprogramming the tumor microenvironment by intervening in RNS production can enhance the efficacy of immune-based treatments.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
William P. Duggan, Batuhan Kisakol, Emer O'Connell, Anna Matveeva, Tony O'Grady, Elizabeth McDonough, Andreas U. Lindner, Deborah McNamara, Daniel Longley, Fiona Ginty, John P. Burke, Jochen H. M. Prehn
Summary: This study investigated the immune properties of mucinous rectal cancer and the degree of lymphocyte infiltration in this type of cancer. The results showed that mucinous rectal cancer had a higher number of cytotoxic and regulatory T cells compared to nonmucinous rectal cancer. The expression of programmed cell death protein 1 was also higher in mucinous rectal cancer. Despite the presence of mucin, the tumor epithelium in mucinous rectal cancer showed higher expressions of CD3 and CD8, suggesting adequate immune infiltration. The importance of this study is rated 8 out of 10.
DISEASES OF THE COLON & RECTUM
(2023)
Article
Immunology
Fangfang Xu, Tingwei Liu, Zhuonan Zhou, Chang Zou, Shaohua Xu
Summary: The study identified APOBEC3A as a protective factor and a promising prognostic biomarker for forecasting the survival and immunotherapy effect of OC patients, potentially accelerating the clinical application and improving immunotherapy effect.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Zhengting Jiang, Wenjie Zhang, Zhilin Zhang, Gengyu Sha, Daorong Wang, Dong Tang
Summary: Pancreatic cancer is a growing cause of cancer-related deaths, often diagnosed at advanced stages. Conventional treatments have poor results, making it difficult to treat. Microbiota and their products have shown promise in regulating pancreatic tumor microenvironment, cancer cell behavior, and immune system functionality. This review summarizes the mechanisms of intratumoral microbiota in pancreatic cancer, highlighting their potential in diagnosis and treatment. Additionally, future prospects for intratumoral microbiota in treating pancreatic cancer are discussed.
Article
Oncology
Daniela Hirsch, Timo Gaiser, Kirsten Merx, Simone Weingaertner, Michael Forster, Alexander Hendricks, Matthias Woenckhaus, Thomas Schubert, Ralf-Dieter Hofheinz, Deniz Gencer
Summary: This study assessed the tumor mutation burden (TMB) as a response marker in six patients with metastatic MSI-H/dMMR gastrointestinal (GI) cancers treated with immune checkpoint inhibitors. While objective radiographic responses were observed in all patients, TMB did not show a clear association with the depth and duration of response. The study highlights the clinical benefit of immune checkpoint blockade in this patient population and the complexity of using TMB as a predictive marker for treatment response.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Immunology
Jinfeng Zhu, Hong Teng, Xiaojian Zhu, Jingxuan Yuan, Qiong Zhang, Yeqing Zou
Summary: KLF3, a key transcriptional repressor, plays significant roles in various biological functions and is particularly important in pancreatic cancer. Abnormal expression of KLF3 is found in multiple tumors and silencing KLF3 expression inhibits pancreatic cancer progression. It is involved in immune-related pathways and tumor progression-related pathways.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Maria Perez-Penco, Stine Emilie Weis-Banke, Aimilia Schina, Majken Siersbaek, Mie Linder Hubbe, Mia Aaboe Jorgensen, Ines Lecoq, Lucia Lara de la Torre, Simone Kloch Bendtsen, Evelina Martinenaite, Morten Orebo Holmstrom, Daniel Hargbol Madsen, Marco Donia, Niels Odum, Lars Grontved, Mads Hald Andersen
Summary: This study demonstrates the antitumor activity of TGF beta-derived multipeptide vaccination in a murine tumor model of PDAC. The vaccine targets immunosuppression and fibrosis in the TME by polarizing the cellular composition towards a more pro-inflammatory phenotype.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Li Qiang, Megan T. Hoffman, Lestat R. Ali, Jaime I. Castillo, Lauren Kageler, Ayantu Temesgen, Patrick Lenehan, S. Jennifer Wang, Elisa Bello, Victoire Cardot-Ruffino, Giselle A. Uribe, Annan Yang, Michael Dougan, Andrew J. Aguirre, Srivatsan Raghavan, Marc Pelletier, Viviana Cremasco, Stephanie K. Dougan
Summary: TGFb blockade enhances chemosensitivity in pancreatic cancer by promoting a classical malignant cell state, providing a scientific rationale for combination therapy with NIS793 and FOLFIRINOX or gemcitabine/nanoparticle (albumin-bound) paclitaxel chemotherapy backbone.