Article
Oncology
MacLean S. Hall, Jamie K. Teer, Xiaoqing Yu, Holly Branthoover, Sebastian Snedal, Madeline Rodriguez-Valentin, Luz Nagle, Ellen Scott, Ben Schachner, Patrick Innamarato, Amy M. Hall, Jamie Blauvelt, Carolyn J. Rich, Allison D. Richards, Jake Ceccarelli, T. J. Langer, Sean J. Yoder, Matthew S. Beatty, Cheryl A. Cox, Jane L. Messina, Daniel Abate-Daga, James J. Mule, John E. Mullinax, Amod A. Sarnaik, Shari Pilon-Thomas
Summary: This study highlights the importance of neoantigen-specific CD4(+)T cells within tumor-infiltrating lymphocytes (TILs) as a potent source of tumor-specific effectors. The findings suggest that these CD4(+)T cells play a significant role in antitumor immunity and should be included in future adoptive cell therapy (ACT) protocols to improve treatment efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Aleksey K. Molodtsov, Nikhil Khatwani, Jennifer L. Vella, Kathryn A. Lewis, Yanding Zhao, Jichang Han, Delaney E. Sullivan, Tyler G. Searles, Nicholas K. Preiss, Tamer B. Shabaneh, Peisheng Zhang, Aaron R. Hawkes, Brian T. Malik, Fred W. Kolling, Edward J. Usherwood, Sandra L. Wong, Joseph D. Phillips, Keisuke Shirai, Christina Angeles, Shaofeng Yan, Tyler J. Curiel, Yina H. Huang, Chao Cheng, Mary Jo Turk
Summary: The study revealed that tumor-specific Trm cells persist in lymph nodes, restraining the development of metastatic cancer and providing long-term protection against melanoma seeding. These findings suggest that Trm cells play a crucial role in preventing the spread of melanoma.
Article
Oncology
Jordan W. Conway, Robert Rawson, Serigne Lo, Tasnia Ahmed, Ismael A. Vergara, Tuba N. Gide, Grace Heloise Attrill, Matteo S. Carlino, Robyn P. M. Saw, John F. Thompson, Andrew J. Spillane, Kerwin F. Shannon, Brindha Shivalingam, Alexander Maxwell Menzies, James S. Wilmott, Georgina Long, Richard A. Scolyer, Ines Pires da Silva
Summary: This study aimed to compare the tumor immune microenvironment of melanoma metastases in different anatomical sites. The results showed that liver and brain metastases had lower immune infiltrate, which may contribute to poorer prognosis and reduced response to immunotherapy. Additionally, increased TIM-3 expression in liver metastases suggests a potential therapeutic opportunity for improving patient outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Andrea M. Amitrano, Brandon J. Berry, Kihong Lim, Kyun-Do Kim, Richard E. Waugh, Andrew P. Wojtovich, Minsoo Kim
Summary: Cancer immunotherapy is more effective against hematological malignancies than solid tumors due to metabolic challenges in the tumor microenvironment. Mitochondria play a key role in CD8(+) T cell activation and effector function. Enhanced mitochondrial function is associated with improved T cell migration and effector function, highlighting the importance of mitochondrial metabolism in T cell responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Anastasia Gangaev, Elisa A. Rozeman, Maartje W. Rohaan, Olga I. Isaeva, Daisy Philips, Sanne Patiwael, Joost H. van den Berg, Antoni Ribas, Dirk Schadendorf, Bastian Schilling, Ton N. Schumacher, Christian U. Blank, John B. A. G. Haanen, Pia Kvistborg
Summary: PD-1 blockade may primarily affect T cell composition in peripheral blood, while CTLA-4 blockade may result in the expansion of melanoma-reactive CD8 T cell response in peripheral blood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Saeed Daneshmandi, Teresa Cassel, Penghui Lin, Richard M. Higashi, Gerburg M. Wulf, Vassiliki A. Boussiotis, Teresa W-M Fan, Pankaj Seth
Summary: Genetic ablation or pharmacologic inhibition of the PPP enzyme 6PGD enhances the generation of potent CD8(+) T effector cells, which show strong anti-tumor functions through metabolic reprogramming and balancing ROS production.
Article
Oncology
Katarina Pinjusic, Olivier Andreas Dubey, Olga Egorova, Sina Nassiri, Etienne Meylan, Julien Faget, Daniel Beat Constam
Summary: This study reveals that Activin-A secretion by melanoma cells inhibits adaptive antitumor immunity by indirectly inhibiting CD8(+) T cell infiltration, regardless of BRAF status. It is also found that Activin-A/INHBA expression is correlated with resistance to anti-PD1 therapy in melanoma patients and impairs response to combination anti-cytotoxic T-Lymphocyte associated protein 4/anti-PD1 treatment in preclinical models.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
David O. 'Sullivan, Michal A. Stanczak, Matteo Villa, Franziska M. Uhl, Mauro Corrado, Ramon I. Klein Geltink, David E. Sanin, Petya Apostolova, Nisha Rana, Joy Edwards-Hicks, Katarzyna M. Grzes, Agnieszka M. Kabat, Ryan L. Kyle, Mario Fabri, Jonathan D. Curtis, Michael D. Buck, Annette E. Patterson, Annamaria Regina, Cameron S. Field, Francesc Baixauli, Daniel J. Puleston, Edward J. Pearce, Robert Zeiser, Erika L. Pearce
Summary: Fever can enhance metabolic activity and effector functions of activated CD8* T cells, with limited effects on proliferation or activation marker expression. Exposure to 39 degrees Celsius increases mass and metabolism in T cells, with mitochondrial translation playing a crucial role in the enhanced metabolic activity and function observed.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Marko Sustic, Maja Cokaric Brdovcak, Berislav Lisnic, Jelena Materljan, Vanda Juranic Lisnic, Carmen Rozmanic, Daniela Indenbirken, Lea Hirsl, Dirk H. Busch, Ilija Brizic, Astrid Krmpotic, Stipan Jonjic
Summary: CMV vectors have the potential to induce strong immune responses, with RAE-1 gamma MCMV showing enhanced immunoprotection against bacterial and tumor challenges. The phenotypic and functional characteristics of memory CD8 T cells induced by RAE-1 gamma MCMV were distinct compared to control vectors, with differences in cytokine production and cytotoxic potential. Adoptive transfer of cells primed with RAE-1 gamma MCMV led to efficient rejection of established tumors, highlighting the importance of latent infection and cell numbers in enhancing anti-tumor responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Faizah Alotaibi, Mark Vincent, Wei-Ping Min, James Koropatnick
Summary: CD5, a marker for T cells and a subset of B cells, is negatively correlated with anti-tumor activity in lung cancer patients, potentially impairing activation of anti-tumor T cells. T cells with high CD5 levels in tumors and lymphoid organs exhibit higher levels of activation and effector function, indicating that CD5 may be a therapeutic target for immunotherapeutic activation in cancer therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Najmeh Bozorgmehr, Isobel Okoye, Olaide Oyegbami, Lai Xu, Amelie Fontaine, Nanette Cox-Kennett, Loree M. Larratt, Mark Hnatiuk, Andrei Fagarasanu, Joseph Brandwein, Anthea C. Peters, Shokrollah Elahi
Summary: The study found that CD160 was the most upregulated co-inhibitory receptor in patients with CLL, and its expression was associated with an exhausted T cell phenotype. EVs were identified as a source of CD160 in the plasma of CLL patients. Additionally, a dominantly proinflammatory cytokine profile, especially elevated interleukin-16, was observed in CLL patients' plasma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Marija Mojic, Kiyomi Shitaoka, Chikako Ohshima, Sisca Ucche, Fulian Lyu, Hiroshi Hamana, Hideaki Tahara, Hiroyuki Kishi, Yoshihiro Hayakawa
Summary: By analyzing the immunological status of tumor antigen-specific CD8(+) T cells during tumor progression, it was found that NKG2D can control the fate and TOX expression of tumor-reacting CD8(+) T cells.
Article
Immunology
Qiao Liu, Lisha Wang, Huayu Lin, Zhiming Wang, Jialin Wu, Junyi Guo, Shuqiong Wen, Ling Ran, Zhengliang Yue, Xingxing Su, Qing Wu, Jianfang Tang, Zhirong Li, Li Hu, Lifan Xu, Lilin Ye, Qizhao Huang
Summary: Cytotoxic CD8(+) T cells are the main focus of anti-tumor immunity and immunotherapy research, but transferred tumor-specific CD8(+) T cells have limited effect on suppressing tumor growth. On the other hand, CD4(+) T cells play an important role in curtailing tumor metastasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Aenne Harberts, Constantin Schmidt, Joanna Schmid, Daniel Reimers, Friedrich Koch-Nolte, Hans-Willi Mittruecker, Friederike Raczkowski
Summary: IRF4 is essential for the activation and reactivation of CD8(+) memory T cells, but does not affect their overall survival. However, the formation and maintenance of CD8(+) tissue-resident memory T cells appears to depend on IRF4.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Ozge Hurdogan, Francesco De Logu, Francesca Galli, Samuray Tuncer, Filippo Ugolini, Sara Simi, Francesca Portelli, Romina Nassini, Daniela Massi, Nesimi Buyukbabani
Summary: This study used digital pathology and image analysis to predict the prognosis of uveal melanoma (UM). The results showed that a higher intratumoral CD8 positive cell density had a negative impact on both recurrence-free survival (RFS) and overall survival (OS). Older age and stage III were also identified as negative prognostic factors. The distribution profile of CD8 may be used to predict the risk of relapse and death in UMs.
Article
Oncology
Prachi Bhave, Lalit Pallan, Georgina V. Long, Alexander M. Menzies, Victoria Atkinson, Justine V. Cohen, Ryan J. Sullivan, Vanna Chiarion-Sileni, Marta Nyakas, Katharina Kahler, Axel Hauschild, Ruth Plummer, Claudia Trojaniello, Paolo A. Ascierto, Lisa Zimmer, Dirk Schadendorf, Clara Allayous, Celeste Lebbe, Andrea Maurichi, Mario Santinami, Severine Roy, Caroline Robert, Thierry Lesimple, Sapna Patel, Judith M. Versluis, Christian U. Blank, Adnan Khattak, Andre van der Westhuizen, Matteo S. Carlino, Mark Shackleton, Andrew Haydon
Summary: The study found that patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 therapy, with outcomes similar to those seen when first-line anti-PD-1 therapy is used in stage IV melanoma.
BRITISH JOURNAL OF CANCER
(2021)
Meeting Abstract
Oncology
F. De Santis, S. L. Romero-Cordoba, L. Castagnoli, T. Volpari, S. Faraci, G. Fuca, L. Cerchietti, E. Tagliabue, F. De Braud, S. M. Pupa, M. Di Nicola
ANNALS OF ONCOLOGY
(2021)
Review
Oncology
G. Fuca, A. Spagnoletti, M. Ambrosini, F. de Braud, M. Di Nicola
Summary: ICEs are emerging as a feasible alternative to adoptive cell therapy in cancer immunotherapy, but their development in solid tumors remains a challenge. This review focuses on the major obstacles and translational approaches proposed to overcome the limitations of ICEs in solid tumors, serving as a primer for clinicians.
Review
Oncology
Francesco Mainini, Francesca De Santis, Giovanni Fuca, Massimo Di Nicola, Licia Rivoltini, Michael Eccles
Summary: Conventional anti-cancer treatments such as chemotherapy and radiation often have harmful side effects and limited curative effects. Recently, novel treatments like immunotherapy have gained attention for their ability to stimulate the host immune system to fight cancer. Nanoparticle-based delivery systems can enhance drug delivery to tumor sites and work synergistically with other therapies to improve treatment outcomes.
Review
Oncology
Margherita Ambrosini, Giovanni Fuca, Matteo Duca, Silvia Damian, Francesca De Santis, Francesca Corti, Sara Cresta, Filippo de Braud, Massimo Di Nicola
Summary: In the era of precision medicine, targeted protein degraders are emerging biological agents that can overcome treatment resistance and druggability limitations of certain key oncogenic proteins by promoting their specific degradation.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Francesca De Santis, Sandra L. Romero-Cordoba, Lorenzo Castagnoli, Tatiana Volpari, Simona Faraci, Giovanni Fuca, Elda Tagliabue, Filippo De Braud, Serenella M. Pupa, Massimo Di Nicola
Summary: This study investigates the activity and mechanisms of BCL6 in the CSC compartment of TNBC, mainly through Notch signaling, providing insights for the prospective design of combination treatment strategies targeting TNBC-associated biomarkers (such as BCL6) and molecules in developmentally conserved signaling pathways (such as Notch) to achieve long-lasting tumor control and improve patient outcomes.
Article
Oncology
Saveria Tropea, Paolo Del Fiore, Andrea Maurichi, Roberto Patuzzo, Mario Santinami, Simone Ribero, Pietro Quaglino, Virginia Caliendo, Lorenzo Borgognoni, Serena Sestini, Giuseppe Giudice, Eleonora Nacchiero, Corrado Caraco, Adriana Cordova, Nicola Solari, Dario Piazzalunga, Francesca Tauceri, Paolo Carcoforo, Maurizio Lombardo, Sara Cavallari, Simone Mocellin
Summary: This study reviewed a cohort of 2,086 melanoma patients who underwent CLND after a positive SN biopsy, and identified age, gender, Breslow thickness, ulceration, SNTB size, and metastatic NSN as independent negative predictors of OS. The results were used to build a prognostic model for personalized treatment.
Article
Oncology
Prachi Bhave, Tasnia Ahmed, Serigne N. Lo, Alexander Shoushtari, Anne Zaremba, Judith M. Versluis, Joanna Mangana, Michael Weichenthal, Lu Si, Thierry Lesimple, Caroline Robert, Claudia Trojanello, Alexandre Wicky, Richard Heywood, Lena Tran, Kathleen Batty, Florentia Dimitriou, Anna Stansfeld, Clara Allayous, Julia K. Schwarze, Meghan J. Mooradian, Oliver Klein, Inderjit Mehmi, Rachel Roberts-Thomson, Andrea Maurichi, Hui-Ling Yeoh, Adnan Khattak, Lisa Zimmer, Christian U. Blank, Egle Ramelyte, Katharina C. Kaehler, Severine Roy, Paolo A. Ascierto, Olivier Michielin, Paul C. Lorigan, Douglas B. Johnson, Ruth Plummer, Celeste Lebbe, Bart Neyns, Ryan Sullivan, Omid Hamid, Mario Santinami, Grant A. McArthur, Andrew M. Haydon, Georgina Long, Alexander M. Menzies, Matteo S. Carlino
Summary: Acral melanoma is a rare subtype with poor prognosis, and there is a lack of prospective clinical trial evidence on the efficacy of checkpoint inhibitors in this population. The study found that initial anti-PD-1/ipilimumab combination had a significantly higher ORR compared to anti-PD-1 alone, but this benefit did not translate to improved OS in this retrospective cohort. Primary site did not impact treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Claudia Sabato, Teresa Maria Rosaria Noviello, Alessia Covre, Sandra Coral, Francesca Pia Caruso, Zein Mersini Besharat, Elena Splendiani, Laura Masuelli, Cecilia Battistelli, Alessandra Vacca, Giuseppina Catanzaro, Agnese Po, Andrea Anichini, Michele Maio, Michele Ceccarelli, Anna Maria Di Giacomo, Elisabetta Ferretti
Summary: This study aimed to identify a melanoma-specific circulating microRNA signature and evaluate its value as a diagnostic tool. Through validation in three independent cohorts, a panel of highly accurate melanoma-specific circulating microRNAs was identified and validated. Additionally, it was discovered that these microRNAs may have an immune suppressive role in melanoma patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Maria F. Ianno, Veronica Biassoni, Elisabetta Schiavello, Andrea Carenzo, Luna Boschetti, Lorenza Gandola, Barbara Diletto, Edoardo Marchesi, Claudia Vegetti, Alessandra Molla, Christof M. Kramm, Dannis G. van Vuurden, Patrizia Gasparini, Francesca Gianno, Felice Giangaspero, Piergiorgio Modena, Brigitte Bison, Andrea Anichini, Sabina Vennarini, Emanuele Pignoli, Maura Massimino, Loris De Cecco
Summary: This study demonstrates for the first time that circulating nucleic acids in the blood can serve as powerful and easy-to-assay molecular markers for the disease status of diffuse intrinsic pontine glioma (DIPG), providing valuable prognostic information.
Article
Oncology
Anna M. Di Giacomo, Maximilian J. Mair, Michele Ceccarelli, Andrea Anichini, Ramy Ibrahim, Michael Weller, Michael Lahn, Alexander M. M. Eggermont, Bernard Fox, Michele Maio
Summary: The conditions that promote immunotherapy responses in primary or secondary brain malignancies were discussed during the V Siena Immuno-Oncology (IO) Think Tank meeting in 2021. Important publications in 2021 and 2022 have reinforced the core elements of these discussions. While current immunotherapies have failed to benefit patients with primary brain tumors like glioblastoma, they have shown positive responses in brain metastases. The differences between these conditions seem to be influenced by intrinsic and extrinsic factors, such as driver mutations, the blood-brain barrier, and the immune suppressive microenvironment. Future therapeutic interventions may focus on rebalancing the immune cell population to enable better responses to current and future immunotherapies.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Andrea Anichini, Alessandra Molla, Gabriella Nicolini, Valentina Eleonora Perotti, Francesco Sgambelluri, Alessia Covre, Carolina Fazio, Maria Fortunata Lofiego, Anna Maria Di Giacomo, Sandra Coral, Antonella Manca, Maria Cristina Sini, Marina Pisano, Teresa Noviello, Francesca Caruso, Silvia Brich, Giancarlo Pruneri, Andrea Maurichi, Mario Santinami, Michele Ceccarelli, Giuseppe Palmieri, Michele Maio, Roberta Mortarini
Summary: This study investigated the effects of different classes of epigenetic drugs on gene expression in melanoma cells. The DNMT inhibitor guadecitabine showed the most promising immunomodulatory activity, particularly in upregulating immune-related genes. Activation of guadecitabine-specific upstream regulator (UR) signature molecules in tumor biopsies predicted treatment response in patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Giuseppe Lo Russo, Monica Ganzinelli, Francesco Sgambelluri, Francesca Galli, Arsela Prelaj, Sara Manglaviti, Achille Bottiglieri, Rosa Maria Di Mauro, Roberto Ferrara, Andra Diana Dumitrascu, Elisa Sottotetti, Antonia Martinetti, Alessandra Fabbri, Eliana Rulli, Filippo G. De Braud, Valter Torri, Marina Chiara Garassino, Andrea Anichini, Claudia Proto, Roberta Mortarini
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Marina Chiara Garassino, Claudia Proto, James M. Dolezal, Arsela Prelaj, Luca Agnelli, Tiziana Triulzi, Alessandra Fabbri, Roberto Ferrara, Francesco Sgambelluri, Tommaso Torelli, Silvia Brich, Sara Manglaviti, Andrea Anichini, Roberta Mortarini, Giorgio Trinchieri, Giancarlo Pruneri, Filippo G. De Braud, Valter Torri, Monica Ganzinelli, Giuseppe Lo Russo
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
M. Mandala, P. Rutkowski, F. Galli, R. Patuzzo, V. De Giorgi, E. Rulli, A. Gianatti, B. Valeri, B. Merelli, A. Szumera-Cieckiewicz, D. Massi, A. Maurichi, P. Teterycz, M. Santinami
Summary: Acral lentiginous melanoma (ALM) has a negative impact on disease-free survival (DFS) in patients. These findings have important clinical implications for patient stratification in future clinical trials and the AJCC classification.