Article
Oncology
Ravikumar Muthuswamy, A. J. Robert McGray, Sebastiano Battaglia, Wenjun He, Anthony Miliotto, Cheryl Eppolito, Junko Matsuzaki, Tsuji Takemasa, Richard Koya, Thinle Chodon, Brian D. Lichty, Protul Shrikant, Kunle Odunsi
Summary: Resident memory CD8 T cells, characterized by their ability to reside in peripheral tissues, play a crucial role in adaptive sentinel activity and amplifying immune responses. The study focused on the chemotactic mechanisms governing the localization, retention, and residency of memory CD8 T cells in the ovarian tumor microenvironment. Results indicated that CXCR6 is a key marker for resident memory tumor-specific CD8 T cells, with its deficiency resulting in reduced retention in tumor tissues and poor control of ovarian cancer. Further research is needed to explore the potential of utilizing CXCR6 to enhance resident memory responses in cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
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)
Review
Biochemistry & Molecular Biology
Nagaja Capitani, Laura Patrussi, Cosima T. Baldari
Summary: The tumor microenvironment, like the two-faced god Janus in Roman mythology, exhibits opposing activities where immune cells fight against tumor cells yet also contribute to their proliferation and spread, particularly cytotoxic T cells which can become exhausted during their killing activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Grace Heloise Attrill, Carina N. Owen, Tasnia Ahmed, Ismael A. Vergara, Andrew J. Colebatch, Jordan W. Conway, Kazi J. Nahar, John F. Thompson, Ines Pires da Silva, Matteo S. Carlino, Alexander M. Menzies, Serigne Lo, Umaimainthan Palendira, Richard A. Scolyer, Georgina Long, James S. Wilmott
Summary: This study found that specific subsets of CD8+ T cells were significantly associated with recurrence in high-risk patients with stage III melanoma treated with anti-PD-1 therapy. CD39+ tumor-resident memory cells were more prevalent in recurrence-free patients, while bystander T cells were more prevalent in patients who developed recurrence. The CD39+ Trms were located significantly closer to melanoma cells compared to bystander T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Rui Yan, Jianjian Li, Zeru Xiao, Xiaona Fan, Heshu Liu, Ying Xu, Ruya Sun, Jian Liu, Jiannan Yao, Guangyu An, Yan Shi, Yang Ge
Summary: This study found that the gastrointestinal cancer stem cell marker DCLK1 is strongly associated with poor outcomes in colorectal cancer. In vivo experiments confirmed that DCLK1 promotes tumor growth and inhibits the host's antitumor response by recruiting T-cell-suppressive MDSCs. These findings provide a precise therapeutic target for related clinical interventions.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Immunology
Morgane Boulch, Marine Cazaux, Yann Loe-Mie, Ronan Thibaut, Beatrice Corre, Fabrice Lemaitre, Capucine L. Grandjean, Zacarias Garcia, Philippe Bousso
Summary: Chimeric antigen receptor (CAR) T cell therapy relies on interactions with the tumor microenvironment (TME) for optimal activity, with IFN-gamma playing a crucial role in enhancing host immune response and sustaining CAR T cell cytotoxicity. CAR T cell-derived IFN-gamma facilitates host interleukin-12 production to support host immune and CAR T cell responses, highlighting the importance of cytokine-mediated cross-talk for effective CAR T cell therapy.
SCIENCE IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Sohini Banerjee, Uma Nahar, Divya Dahiya, Soham Mukherjee, Pranab Dey, Rijuneeta Gupta, Bishan Radotra, Naresh Sachdeva, Ashwani Sood, Sanjay Kumar Bhadada, Anil Bhansali
Summary: This study aimed to define the tumor microenvironment (TME) of papillary thyroid carcinomas (PTCs) by characterizing the tumor-infiltrating lymphocytes (TILs). The results showed a high presence of CD8(+) cytotoxic T lymphocytes (CTLs) and FoxP3(+) T regulatory cells (Tregs) in PTC cases with lymphocytic thyroiditis (LT). Flow cytometry and immunohistochemistry analysis revealed an association between PD-1/PD-L1 expression and lymph node metastasis and the presence of Treg cells.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Hao Tian, Wenxi Li, Guohao Wang, Ye Tian, Jie Yan, Songtao Zhou, Xinying Yu, Bei Li, Yunlu Dai
Summary: Intratumoral CD8(+) T cells play a crucial role in cancer immunotherapy, but the immunosuppressive tumor microenvironment (TME) limits their function and infiltration. Drug repurposing has identified existing drugs as immune modulators to improve TME immunosuppression and reactivate T-cell-mediated antitumor immunity. However, the suboptimal availability of these drugs in tumors hampers their full immunomodulatory potential. Self-degradable PMI nanogels carrying repurposed immune modulators (imiquimod and metformin) are developed for TME-responsive drug release. They remodel the TME by promoting dendritic cell maturation, repolarizing M2-like tumor-associated macrophages, and downregulating PD-L1 expression. Ultimately, the PMI nanogels reshape the immunosuppressive TME and efficiently enhance CD8(+) T cell infiltration and activation. These results suggest that PMI nanogels could be an effective combination drug with anti-PD-1 antibodies to enhance antitumor immune responses.
Article
Oncology
Stine Emilie Weis-Banke, Thomas Landkildehus Lisle, Maria Perez-Penco, Aimilia Schina, Mie Linder Hubbe, Majken Siersbaek, Morten Orebo Holmstrom, Mia Aaboe Jorgensen, Inge Marie Svane, Ozcan Met, Niels Odum, Daniel Hargbol Madsen, Marco Donia, Lars Grontved, Mads Hald Andersen
Summary: This study identified the presence of ARG2-specific CD8(+) T cells in both healthy donors and patients with cancer. These T cells are capable of recognizing and responding to cancer cells and activated Tregs with high ARG2 expression. Furthermore, vaccination with ARG2-derived epitopes in a mouse tumor model resulted in tumor growth suppression and antitumorigenic immunomodulation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Lijiang Gu, Yuhang Chen, Xing Li, Yibo Mei, Jinlai Zhou, Jianbin Ma, Mengzhao Zhang, Tao Hou, Dalin He, Jin Zeng
Summary: This study analyzed the role of RNA-binding proteins (RBPs) in bladder cancer (BC) and identified six RBPs that may serve as predictors of BC. By analyzing clinical information and RNA sequencing data, RBPs associated with patient survival were identified. The study also found that the expression of four RBPs was significantly upregulated in BC tissues and cell lines. A prognostic model based on these six RBPs was developed and functionally validated.
Article
Biotechnology & Applied Microbiology
Felix J. Hartmann, Dunja Mrdjen, Erin McCaffrey, David R. Glass, Noah F. Greenwald, Anusha Bharadwaj, Zumana Khair, Sanne G. S. Verberk, Alex Baranski, Reema Baskar, William Graf, David Van Valen, Jan Van den Bossche, Michael Angelo, Sean C. Bendall
Summary: This antibody-based method allows profiling of metabolic protein expression and regulation in single cells using mass spectrometry while characterizing cellular phenotype. The approach was validated using mass cytometry and applied to clinical samples, revealing tissue-restricted, metabolically repressed immune cells in human colorectal carcinoma. The combination with multiplexed ion beam imaging unveiled the spatial organization of metabolic programs in human tissues.
NATURE BIOTECHNOLOGY
(2021)
Article
Oncology
Jiang Chang, Songbin Lin, Yihao Mao, Yuqiu Xu, Zhiyuan Zhang, Qi Wu, Yijiao Chen, Ye Wei, Qingyang Feng, Jianmin Xu
Summary: This study investigates the infiltration and prognostic value of CXCR6+TAMs in colon cancer patients and explores its predictive ability as a biomarker for adjuvant chemotherapy regimens. The results showed that high density of CXCR6+ TAM infiltration predicted worse overall survival in all stages of colon cancer. Additionally, a 6-month chemotherapy regimen benefitted high-risk stage II and stage III patients with high CXCR6+ TAM density the most. The study also found a negative relationship between CXCR6+TAMs and activated CD8+ T cells, suggesting a role in the formation of an immunosuppressive environment.
Review
Immunology
Guangna Liu, Wei Rui, Xueqiang Zhao, Xin Lin
Summary: CAR-T cell therapy has shown successful outcomes in hematological malignancies but faces challenges in treating solid tumors due to immunosuppressive mechanisms in the tumor microenvironment. This review summarized inhibitory factors affecting CAR-T cell function and discussed strategies to enhance CAR-T cell efficacy in solid tumor treatment by targeting these barriers.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tomislav Ivanovic, Dorotea Bozic, Benjamin Benzon, Vesna Capkun, Katarina Vukojevic, Merica Glavina Durdov
Summary: Gastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4, and IFN-? in the tumor and regional lymph node (LN) of patients with GC and found correlations between PD-L1 expression and tumor type, CD8+ T cells, and macrophages, as well as between IFN-? expression and CTLA4(+) lymphocytes. Overall survival was negatively correlated with IFN-? expression in metastases. Rating: 8/10.
Article
Oncology
Binglin Wang, Yi Wang, Xiaofan Sun, Guoliang Deng, Wei Huang, Xingxin Wu, Yanghong Gu, Zhigang Tian, Zhimin Fan, Qiang Xu, Hongqi Chen, Yang Sun
Summary: This study revealed that CXCR6 is exclusively expressed on intratumoral CD8(+) T cells, which are more immunocompetent and possess stronger antitumor activity. Additionally, CXCR6 may serve as a biomarker for tumor immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Zsofia D. Drobni, Olivier Michielin, Thiago Quinaglia, Daniel A. Zlotoff, Leyre Zubiri, Hannah K. Gilman, Sama Supraja, Bela Merkely, Veronika Muller, Ryan J. Sullivan, Kerry L. Reynolds, Michael J. Pittet, Rakesh K. Jain, Tomas G. Neilan
Summary: This retrospective study investigated the association between the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and outcomes in patients treated with immune checkpoint inhibitors (ICIs). The results showed that hypertension patients who concomitantly took a RAAS inhibitor during ICI therapy had better overall survival. This benefit was particularly significant among patients with gastrointestinal and genitourinary cancers.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Immunology
Daniela F. Quail, Borko Amulic, Monowar Aziz, Betsy J. Barnes, Evgeniy Eruslanov, Zvi G. Fridlender, Helen S. Goodridge, Zvi Granot, Andres Hidalgo, Anna Huttenlocher, Mariana J. Kaplan, Ilaria Malanchi, Taha Merghoub, Etienne Meylan, Vivek Mittal, Mikael J. Pittet, Andrea Rubio-Ponce, Irina A. Udalova, Timo K. van den Berg, Denisa D. Wagner, Ping Wang, Arturo Zychlinsky, Karin E. de Visser, Mikala Egeblad, Paul Kubes
Summary: This article discusses the functional states and heterogeneity of neutrophils in cancer and provides a consensus statement on the controversies and solutions in neutrophil research. Further research is needed to understand the role of neutrophils in cancer and explore potential novel opportunities for cancer treatment.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Jina Ko, Martin Wilkovitsch, Juhyun Oh, Rainer H. Kohler, Evangelia Bolli, Mikael J. Pittet, Claudio Vinegoni, David B. Sykes, Hannes Mikula, Ralph Weissleder, Jonathan C. T. Carlson
Summary: SAFE is a method for comprehensive longitudinal imaging of living cells using immunofluorescence, allowing multiparameter temporal and spatial imaging. It is non-toxic and functional in various living samples.
NATURE BIOTECHNOLOGY
(2022)
Correction
Oncology
Mikael J. Pittet, Olivier Michielin, Denis Migliorini
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Review
Oncology
Mikael J. Pittet, Olivier Michielin, Denis Migliorini
Summary: The interaction of tumour-associated macrophages (TAMs) with cancer and stromal cells in the tumour microenvironment enables and sustains most of the hallmarks of cancer. The authors of this Review examine the diversity of TAMs in various cancer indications, which is being revisited with the advent of single-cell technologies, and discuss the functional roles of different TAM states, the prognostic and predictive value of TAM-related signatures as well as approaches involving TAMs that are currently being or will soon be tested in clinical trials.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jeremy Gungabeesoon, Nicolas A. Gort-Freitas, Mate Kiss, Evangelia Bolli, Marius Messemaker, Marie Siwicki, Mehdi Hicham, Ruben Bill, Peter Koch, Chiara Cianciaruso, Florent Duval, Christina Pfirschke, Michael Mazzola, Solange Peters, Krisztian Homicsko, Christopher Garris, Ralph Weissleder, Allon M. Klein, Mikael J. Pittet
Summary: Neutrophils accumulate in solid tumors and their abundance is associated with poor prognosis. In this study, the role of neutrophils in immunotherapy and tumor control was investigated. The results demonstrate that successful therapies can expand tumor neutrophil numbers and thereby contribute to antitumor effects.
Article
Oncology
Yves Boucher, Jessica M. Posada, Sonu Subudhi, Ashwin S. Kumar, Spencer R. Rosario, Liqun Gu, Heena Kumra, Mari Mino-Kenudson, Nilesh P. Talele, Dan G. Duda, Dai Fukumura, Jennifer Y. Wo, Jeffrey W. Clark, David P. Ryan, Carlos Fernandez-Del Castillo, Theodore S. Hong, Mikael J. Pittet, Rakesh K. Jain
Summary: In this study, we found that adding losartan (LOS) to FOLFIRINOX (FFX) chemotherapy followed by chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC) resulted in a 61% R0 surgical resection rate. By evaluating the effects of neoadjuvant LOS on the tumor microenvironment, we identified potential mechanisms of benefit. The results showed that LOS+FFX+CRT reduced the expression of immunosuppression and pro-invasion genes and was associated with improved overall survival (OS).
CLINICAL CANCER RESEARCH
(2023)
Correction
Immunology
Vincenzo Bronte, Mikael J. Pittet
Article
Oncology
Lou Romanens, Prasad Chaskar, Rachel Marcone, Stephan Ryser, Jean-Christophe Tille, Raphael Genolet, Ketty Heimgartner-Hu, Killian Heimgartner, Jonathan S. Moore, Nicolas Liaudet, Guerkan Kaya, Mikael J. Pittet, Pierre-Yves Dietrich, Mauro Delorenzi, Daniel E. Speiser, Alexandre Harari, Petros Tsantoulis, Sana Intidhar Labidi-Galy
Summary: The spatial distribution of tumor-infiltrating lymphocytes (TIL) can predict breast cancer outcome and response to treatment. A new method called ST-FFPE has been developed to analyze formalin-fixed paraffin-embedded samples, allowing for the study of archival tissue. By examining different tumor compartments, this method can characterize the cellular composition of the tumor microenvironment.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Laura Fernandez-Rodriguez, Chiara Cianciaruso, Ruben Bill, Marcel P. Trefny, Richard Klar, Nicole Kirchhammer, Melanie Buchi, Julia Festag, Sven Michel, Rainer H. Kohler, Elham Jones, Andre Maaske, Abhishek S. Kashyap, Frank Jaschinski, Karen O. Dixon, Mikael J. Pittet, Alfred Zippelius
Summary: In this study, a high-affinity immunomodulatory IM-T9P1-ASO was developed to target both TLR9 and PD-L1, enhancing the therapeutic efficacy of immune checkpoint inhibitors. The results showed that IM-T9P1-ASO can effectively inhibit tumor growth and promote anti-tumor responses, suggesting its potential importance for cancer treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
David Andreu-Sanz, Sebastian Kobold
Summary: While CD8(+) T cells have been the focus of most cancer immunotherapy approaches, increasing evidence indicates that CD4(+) T cells also play a crucial role in tumor elimination. These T cells can differentiate into different subsets, which have diverse effects on tumor progression depending on the cytokine milieu. This review provides an overview of the role of T helper subsets in the immune system, their implications in cancer immunology, and their applications in adoptive T-cell therapy.
Article
Oncology
Theo Lorenzini, Bruno L. Cadilha, Hannah Obeck, Mohamed-Reda Benmebarek, Florian Maerkl, Stefanos Michaelides, Thaddaeus Strzalkowski, Daria Briukhovetska, Philipp Jie Mueller, Sayantan Nandi, Pia Winter, Lina Majed, Ruth Gruenmeier, Matthias Seifert, Svenja Rausch, Tobias Feuchtinger, Stefan Endres, Sebastian Kobold
Summary: This study investigates the design choices of immunostimulatory fusion protein (IFP) constructs for enhancing the therapeutic efficacy of CAR T cells. It finds that IFP variants with similar extracellular lengths to PD-1 show improved CAR T cell function and proliferation, leading to prolonged survival in a leukemia mouse model. These findings highlight the importance of mimicking the physiological interaction of PD-1 with PD-L1 in IFP design.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Ruben Bill, Pratyaksha Wirapati, Marius Messemaker, Whijae Roh, Beatrice Zitti, Florent Duval, Mate Kiss, Jong Chul Park, Talia M. Saal, Jan Hoelzl, David Tarussio, Fabrizio Benedetti, Stephanie Tissot, Lana Kandalaft, Marco Varrone, Giovanni Ciriello, Thomas A. McKee, Yan Monnier, Maxime Mermod, Emily M. Blaum, Irena Gushterova, Anna L. K. Gonye, Nir Hacohen, Gad Getz, Thorsten R. Mempel, Allon M. Klein, Ralph Weissleder, William C. Faquin, Peter M. Sadow, Derrick Lin, Sara I. Pai, Moshe Sade-Feldman, Mikael J. Pittet
Summary: Tumor microenvironments (TMEs) have an impact on cancer progression and vary between patients. By studying tumor-to-tumor variation, researchers found that macrophage polarity defined by CXCL9 and SPP1 expression had a strong prognostic association. This study suggests that TMEs coordinate coherent responses that control human cancers, with macrophage polarity being a relevant and simple variable.
Article
Dermatology
Stefan Tukaj, Katja Bieber, Wiebke Pruessmann, Jasper N. Pruessmann, Enno Schmidt, Detlef Zillikens, Ralf J. Ludwig, Michael Kasperkiewicz
Summary: Healthy individuals with BP autoantibody reactivity have abnormal vitamin D levels and a specific cytokine profile.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2023)