Article
Cell Biology
Juliane Schuhmacher, Leon Kleemann, Jennifer Rebecca Richardson, Elisa Rusch, Hans-Georg Rammensee, Cecile Gouttefangeas
Summary: Elongated peptides (EPs) are widely used for screening immune cell responses, and this study presents an in vitro protocol for their amplification and functional analysis. It was found that the elongation site of EPs affected the response of CD8(+) T cells, while CD4(+) T cell responses were completely lost in some tests. However, the use of short-term amplification and a TLR3 agonist significantly improved the detection of both CD8(+) and CD4(+) T cell reactivities.
Review
Pharmacology & Pharmacy
Qin Xie, Jian Ding, Yi Chen
Summary: CD8(+) T lymphocytes play a crucial role in host antitumor immunity, but tumor-driven microenvironments can inhibit their activation and cytotoxicity. Stromal cells exert immunosuppressive effects in the tumor microenvironment.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Immunology
Grainne Jameson, Cathal Harmon, Rhyla Mae Santiago, Diarmaid D. Houlihan, Tom K. Gallagher, Lydia Lynch, Mark W. Robinson, Cliona O'Farrelly
Summary: Liver-resident CD56(bright)CD16(-) natural killer (NK) cells may contribute to immune tolerance during liver transplantation. RNA sequencing revealed that these liver-resident NK cells upregulated genes associated tissue residency and expressed immune receptors capable of activating NK cells. Functional assays demonstrated that hepatic NK cells had cytotoxic effects on allogenic CD8(+) T cells, with CD8(+) T cells being more susceptible than CD4(+) T cells, and this cytotoxic response could be enhanced by an anti-CD160 agonist.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Pedro Velica, Pedro P. Cunha, Nikola Vojnovic, Iosifina Petrina Foskolou, David Bargiela, Milos Gojkovic, Helene Rundqvist, Randall S. Johnson
Summary: By ectopically expressing the HIF transcription factor in CD8(+) T cells, this study demonstrated an enhanced antitumor efficacy against tumor targets. A specific mutation in HIF2 alpha showed the most effective antitumor T cell response, suggesting a potential strategy to increase therapeutic efficacy of CD8(+) T cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Laura Llao-Cid, Philipp M. Roessner, Vicente Chapaprieta, Selcen Oeztuerk, Tobias Roider, Marie Bordas, Ana Izcue, Dolors Colomer, Sascha Dietrich, Stephan Stilgenbauer, Bola Hanna, Jose Ignacio Martin-Subero, Martina Seiffert
Summary: The EOMES SNP is associated with increased risk for CLL due to its negative impact on CD8(+) T-cell-mediated immune control of the disease. EOMES is essential for the expansion and maintenance of CD8(+) T cells, and thus involved in adaptive immune control of CLL.
Article
Chemistry, Multidisciplinary
Weiwei Wang, Jing Zhao, Changlong Hao, Shudong Hu, Chen Chen, Yi Cao, Zhengyu Xu, Jun Guo, Liguang Xu, Maozhong Sun, Chuanlai Xu, Hua Kuang
Summary: This study discovers the potential of chiral nanomaterials as immunoadjuvants for the prevention and treatment of cancer. Chiral nanoparticles enhance immune response and inhibit tumor growth through the stimulation of specific cell types, showing better therapeutic effects compared to achiral nanoparticles.
ADVANCED MATERIALS
(2022)
Article
Immunology
Davide Moi, Bijun Zeng, Simone A. Minnie, Rituparna Bhatt, Jack Wood, David P. Sester, Roberta Mazzieri, Riccardo Dolcetti
Summary: Suitable methods to assess in vivo immunogenicity and therapeutic efficacy of cancer vaccines in preclinical cancer models are critical to overcome current limitations of cancer vaccines and enhance the clinical applicability of this promising immunotherapeutic strategy. Moreover, multiparametric assays to deeply characterize tumor-induced and therapy-induced immune modulation are relevant to design mechanism-based combination immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Emma C. Reilly, Mike Sportiello, Kris Lambert Emo, Andrea M. Amitrano, Rakshanda Jha, Ashwin B. R. Kumar, Nathan G. Laniewski, Hongmei Yang, Minsoo Kim, David J. Topham
Summary: CD8 T cell memory within lung tissue is highly heterogeneous, with various subsets such as T-CM, T-EM, T-RM, and populations not fitting neatly into these classifications. CD49a-expressing T-RM cells exhibit increased and diverse effector potential, functioning as a versatile group with antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targets.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Tarun Tyagi, Kanika Jain, Timur O. Yarovinsky, Michael Chiorazzi, Jing Du, Cecilia Castro, Jules Griffin, Asawari Korde, Kathleen A. Martin, Shervin S. Takyar, Richard A. Flavell, Abhijit A. Patel, John Hwa
Summary: This study reveals the immunosuppressive role of platelets in tumor growth and identifies the platelet protein TLT-1 as a key player in suppressing CD8 T cells. Anti-TLT-1 antibody shows potential as a therapeutic option to rescue T cell function and reduce tumor size. Clinically, higher TLT-1 levels are associated with reduced survival in non-small cell lung cancer patients.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Jessica M. Sierra, Florencia Secchiari, Sol Y. Nunez, Ximena L. Raffo Iraolagoitia, Andrea Ziblat, Adrian D. Friedrich, Maria V. Regge, M. Cecilia Santilli, Nicolas I. Torres, Mariana Gantov, Aldana Trotta, Carlos Ameri, Gonzalo Vitagliano, Hernando Rios Pita, Luis Rico, Agustin Rovegno, Nicolas Richards, Carolina I. Domaica, Norberto W. Zwirner, Mercedes B. Fuertes
Summary: NK cells in clear cell renal cell carcinoma patients display altered phenotype and impaired effector functions, with a high frequency of tumor-infiltrating PD-L1(+) NK cells suggesting immunoregulatory functions. In vitro studies show that PD-L1(hi) NK cells exhibit an activated phenotype and enhanced effector functions, while also inhibiting CD8(+) T cell proliferation in a PD-L1-dependent manner.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Siyu Liu, Chang Xu, Fan Yang, Lu Zong, Yizu Qin, Yufeng Gao, Qian Su, Tuantuan Li, Ye Li, Yuanhong Xu, Meijuan Zheng
Summary: The antiviral response of NK cells and CD8(+) T cells is weak in patients with CHB, and the overexpression of Gal-9 contributes to NK cell dysfunction and CD8(+) T cell exhaustion. Blocking Gal-9 or TIM-3 can restore the function of CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Mikiya Tsunoda, Hiroyasu Aoki, Haruka Shimizu, Shigeyuki Shichino, Kouji Matsushima, Satoshi Ueha
Summary: Temporal analysis of T cell receptor (TCR) repertoire is important for monitoring changes in antigen-specific T cells in cancer patients. However, lack of experimental models for temporal analysis within a homogeneous population limits understanding of the relationship between TCR repertoire changes and antitumor responses. Bilateral tumor model showed highly similar T-cell clones in bilateral tumors and different patterns in draining lymph nodes, suggesting independent induction of tumor-reactive T cell clones in each lymph node.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Breanna M. Scorza, Kurayi G. Mahachi, Arin D. Cox, Angela J. Toepp, Danielle Pessoa-Pereira, Phyllis Tyrrell, Jesse Buch, Jennifer A. Foltz, Dean Lee, Christine A. Petersen
Summary: The study found that asymptomatic dogs exposed to Borrelia burgdorferi had elevated levels of serum interleukin-21 and increased circulating CD3(+) CD94(+) lymphocytes. On the other hand, symptomatic dogs had higher expression of gamma interferon upon stimulation with B. burgdorferi. Additionally, an NK-like CD8(+) T cell response was linked to protection against clinical Lyme disease, while excess IFN-gamma was associated with clinical disease.
INFECTION AND IMMUNITY
(2022)
Article
Immunology
Dmytro Shytikov, Deepak Rohila, Dan Li, Pengfei Wang, Mei Jiang, Mingxu Zhang, Qin Xu, Linrong Lu
Summary: The role of Ly49(+)CD8 T-cells in the immune system and the mechanism of Ly49 expression on CD8 T-cells are still unclear. Studies have shown that Ly49(+)CD8 T-cells express different receptors compared to NK cells and play important roles in immune response and viral infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sihan Wu, Xuan Zhang, Cuiping Hu, Yajie Zhong, Jun Chen, Wai Po Chong
Summary: This study found that the activation of CD8(+) T cells significantly suppressed the cytokine production of Th1 and Th17 cells, and this treatment had a therapeutic effect in experimental autoimmune uveitis. Additionally, IFN-gamma(+) CD8(+) T cells were recruited more efficiently into lymphoid organs during the disease-priming phase, and this recruitment depended on the CXCR3 receptor.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Elena Muraro, Mariangela De Zorzi, Gianmaria Miolo, Davide Lombardi, Simona Scalone, Simon Spazzapan, Samuele Massarut, Tiziana Perin, Riccardo Dolcetti, Agostino Steffan, Valli De Re
Summary: This study investigates the impact of host immune genetics on the response to trastuzumab treatment in HER2-positive breast cancer patients. The results suggest that patients with KIR haplotype tel B have higher ADCC efficiency, while the presence of KIR3DL2/HLA-A03 or A11 is associated with poorer prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Jenny Dunn, Robert D. McCuaig, Abel H. Y. Tan, Wen Juan Tu, Fan Wu, Kylie M. Wagstaff, Anjum Zafar, Sayed Ali, Himanshu Diwakar, Jane E. Dahlstrom, Elaine G. Bean, Jade K. Forwood, Sofiya Tsimbalyuk, Emily M. Cross, Kristine Hardy, Amanda L. Bain, Elizabeth Ahern, Riccardo Dolcetti, Roberta Mazzieri, Desmond Yip, Melissa Eastgate, Laeeq Malik, Peter Milburn, David A. Jans, Sudha Rao
Summary: The study found that a protein called nPKC-theta is enriched in circulating tumor cells (CTCs) in patients with triple-negative breast cancer (TNBC) brain metastases and immunotherapy-resistant metastatic melanoma, and is associated with poor survival in immunotherapy-resistant disease. A novel nPKC-theta inhibitor was designed to target nPKC-theta and showed potential in reducing mesenchymal cancer stem cell signatures in immunotherapy-resistant CTCs and TNBC xenografts.
Article
Oncology
Michela Cangemi, Marcella Montico, Marco Trovo, Emilio Minatel, Emanuela Di Gregorio, Giuseppe Corona, Fabiana Giordari, Elisa Comaro, Francesca Colizzi, Lorena Baboci, Agostino Steffan, Alberto Revelant, Elena Muraro
Summary: The study evaluated the immune profile and effects of radical hemithoracic radiation therapy (RT) in patients with malignant pleural mesothelioma (MPM) and identified potential predictive biomarkers for therapy response and toxicity development. Blood samples were collected and immunomonitoring was performed before, during, and after RT to assess immune parameters. The results showed significant improvements in activated T cells and interferon-g-producing cells after RT. High levels of Th22 and IL-10 at baseline were associated with improved survival, while an increase in serum mesothelin was correlated with severe toxicity. The study suggests the potential synergistic effect of RT and immunotherapeutic treatment.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Virology
Giulia Brisotto, Marcella Montico, Matteo Turetta, Stefania Zanussi, Maria Rita Cozzi, Roberto Vettori, Romina Boschian Boschin, Lorenzo Vinante, Fabio Matrone, Alberto Revelant, Elisa Palazzari, Roberto Innocente, Giuseppe Fanetti, Lorenzo Gerratana, Mattia Garutti, Camilla Lisanti, Silvia Bolzonello, Milena Sabrina Nicoloso, Agostino Steffan, Elena Muraro
Summary: Cellular and humoral immunity are both crucial in SARS-CoV-2 infection recovery and vaccine efficacy. The impact of mRNA vaccination on immune responses in healthy and fragile individuals is still being investigated. This study examined the cellular and humoral immune responses after vaccination in healthy subjects and cancer patients to assess antibody levels, cellular immunity, and the influence of cancer on vaccination efficacy. The findings highlight the correlation between higher antibody titers and positive cellular immunity, as well as the stability of T-cell responses over time compared to antibody levels, particularly in cancer patients.
Review
Genetics & Heredity
Mattia Garutti, Lorenzo Foffano, Roberta Mazzeo, Anna Michelotti, Lucia Da Ros, Alessandra Viel, Gianmaria Miolo, Alberto Zambelli, Fabio Puglisi
Summary: Hereditary cancer syndromes, though often underdiagnosed, account for nearly 10% of cancers. Identifying pathogenic gene variants could have significant implications for treatment, prevention, and testing, but diagnosing these syndromes can be challenging due to lack of validated criteria and suboptimal performance. Many clinicians are not adequately trained to select patients for genetic testing. This review categorizes hereditary cancer syndromes affecting adults and provides a visual tool to help clinicians in their daily practice.
Article
Immunology
Davide Moi, Bijun Zeng, Simone A. Minnie, Rituparna Bhatt, Jack Wood, David P. Sester, Roberta Mazzieri, Riccardo Dolcetti
Summary: Suitable methods to assess in vivo immunogenicity and therapeutic efficacy of cancer vaccines in preclinical cancer models are critical to overcome current limitations of cancer vaccines and enhance the clinical applicability of this promising immunotherapeutic strategy. Moreover, multiparametric assays to deeply characterize tumor-induced and therapy-induced immune modulation are relevant to design mechanism-based combination immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Elena Muraro, Lorenzo Vinante, Elisabetta Fratta, Alessandra Bearz, Daniela Hoefler, Agostino Steffan, Lorena Baboci
Summary: Metronomic chemotherapy is an alternative approach for cancer treatment, which involves continuous administration of low-dose drugs to overcome drug resistance and toxic side effects. It can control tumor growth by inhibiting angiogenesis, suppressing tumor cell growth, and enhancing immune response. Combining metronomic chemotherapy with immune checkpoint inhibitors has shown synergistic therapeutic effects in preclinical and clinical studies. However, optimal drug combinations, sequence, and concentration-time factors still need to be evaluated in representative preclinical models.
Review
Oncology
Davide Adriano Santeufemia, Giuseppe Palmieri, Gianmaria Miolo, Maria Colombino, Maria Grazia Doro, Laura Frogheri, Panagiotis Paliogiannis, Giampiero Capobianco, Massimo Madonia, Giovanni Lo Re, Antonio Cossu, Giuseppe Corona
Summary: This review summarizes the molecular features, clinical advancements, and therapeutic directions of primary mucosal melanoma (MM), a rare and heterogeneous malignancy with poor prognosis. MM differs significantly from cutaneous melanoma in terms of epidemiology, genetic profile, clinical presentation, and response to therapies. Recent omics techniques have revealed distinct genomic, molecular, and metabolic landscapes of MM lesions compared to cutaneous lesions, which explains the heterogeneity of treatment response. The specific molecular aspects of MM may help identify new biomarkers for improved diagnosis and selection of patients suitable for immunotherapy or targeted therapy.
Review
Oncology
Charlene Waryah, Eric Alves, Roberta Mazzieri, Riccardo Dolcetti, Erik W. Thompson, Andrew Redfern, Pilar Blancafort
Summary: The article reviews the importance of epithelial plasticity in cancer development, discussing the role of epithelial-to-mesenchymal transition (EMT) in cancer metastasis, drug resistance, etc., and introduces the related regulatory factors and treatment strategies.
Article
Oncology
Angela Buonadonna, Simona Scalone, Davide Lombardi, Arianna Fumagalli, Alessandra Guglielmi, Chiara Lestuzzi, Jerry Polesel, Vincenzo Canzonieri, Stefano Lamon, Petros Giovanis, Sara Gagno, Giuseppe Corona, Maurizio Mascarin, Claudio Belluco, Antonino De Paoli, Gianpiero Fasola, Fabio Puglisi, Gianmaria Miolo
Summary: This study investigates the combination of non-pegylated liposomal doxorubicin (NPLD) with ifosfamide as a first-line treatment for advanced/metastatic soft tissue sarcoma (STS). The results show a significant overall response rate and disease control rate, indicating that this drug combination is effective and well-tolerated. This finding provides a basis for further research on the clinical application of this drug combination in STS.
Article
Cell Biology
Bijun Zeng, Davide Moi, Lynn Tolley, Natalie Molotkov, Ian Hector Frazer, Christopher Perry, Riccardo Dolcetti, Roberta Mazzieri, Jazmina L. G. Cruz
Summary: This study successfully established two humanized mouse models that exhibited strong antigen-specific responses and demonstrated tumor regression following vaccination. These models serve as valuable platforms for assessing the efficacy of therapeutic cancer vaccines targeting HPV16-dysplastic skin and diverse tumor antigens specifically delivered to CD141+ DCs.
Article
Biochemistry & Molecular Biology
Gianmaria Miolo, Angela Buonadonna, Simona Scalone, Davide Lombardi, Lara Della Puppa, Agostino Steffan, Giuseppe Corona
Summary: Specific bile acid metabolic profiles may be associated with the prognosis of mSTS patients, while prognostic factors for mSTS are currently very limited.
Review
Oncology
Joshua K. M. Wong, Riccardo Dolcetti, Handoo Rhee, Fiona Simpson, Fernando Souza-Fonseca-Guimaraes
Summary: Enhancing innate immunity through natural killer (NK) cell-based immunotherapy has shown promising results in treating difficult-to-cure solid cancers. Monoclonal antibody (mAb) therapy has been used to activate NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against solid tumors. However, using immunosuppressive mechanisms, cancer cells can evade immunosurveillance and hinder NK cell ADCC. Recent advances in the field include strategies to enhance ADCC by temporarily inhibiting receptor endocytosis and increasing antibody presentation from target to effector cells. This review discusses these advances and highlights the current and potential future use of immunotherapies to maximize the therapeutic efficacy of innate anticancer immunity.
Meeting Abstract
Dermatology
S. Daignault, R. J. Ju, L. Spoerri, S. J. Stehbens, D. S. Hill, R. Dolcetti, N. Haass
EXPERIMENTAL DERMATOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
C. Lestuzzi, I. Cosei, F. Navarria, E. Viel, A. Ravasel, A. Fumagalli, G. M. Miolo, B. Popescu, A. Buonadonna
EUROPEAN HEART JOURNAL
(2022)