Cancer immunotherapy has transformed the treatment landscape for numerous malignancies and is emerging as an increasingly revolutionary and promising approach for cancer treatment.Clustered regularly ...interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) screening, a potent tool for unbiased functional genomic screening, has unveiled novel molecular targets for cancer immunotherapy.CRISPR/Cas9 screening facilitates the identification of targets in both cancer cells and immune cells, including T and natural killer cells.Various CRISPR screening methods such as in vitro and in vivo screening, along with diverse techniques including CRISPR-ko, CRISPRi, and CRISPRa screening, are utilized for target identification across various cancer models.In vivo CRISPR screening replicates human cancer by preserving the native microenvironment and facilitating high-throughput analysis of intricate cancer processes.
Clustered regularly interspaced palindromic repeats (CRISPR)-based technology, a powerful toolset for the unbiased functional genomic screening of biological processes, has facilitated several scientific breakthroughs in the biomedical field. Cancer immunotherapy has advanced the treatment of numerous malignancies that previously had restricted treatment options or unfavorable outcomes. In the realm of cancer immunotherapy, the application of CRISPR/CRISPR-associated protein 9 (Cas9)-based genetic perturbation screening has enabled the identification of genes, biomarkers, and signaling pathways that govern various cancer immunoreactivities, as well as the development of effective immunotherapeutic targets. In this review, we summarize the advances in CRISPR/Cas9-based screening for cancer immunotherapy and outline the immunotherapeutic targets identified via CRISPR screening based on cancer-type classification.
Clustered regularly interspaced palindromic repeats (CRISPR)-based technology, a powerful toolset for the unbiased functional genomic screening of biological processes, has facilitated several scientific breakthroughs in the biomedical field. Cancer immunotherapy has advanced the treatment of numerous malignancies that previously had restricted treatment options or unfavorable outcomes. In the realm of cancer immunotherapy, the application of CRISPR/CRISPR-associated protein 9 (Cas9)-based genetic perturbation screening has enabled the identification of genes, biomarkers, and signaling pathways that govern various cancer immunoreactivities, as well as the development of effective immunotherapeutic targets. In this review, we summarize the advances in CRISPR/Cas9-based screening for cancer immunotherapy and outline the immunotherapeutic targets identified via CRISPR screening based on cancer-type classification.
Correction to: J Transl Med (2020) 18:405 https://doi.org/10.1186/s12967-020-02573-9 Following publication of the original article 1 the authors identified that the collaborators of the TOCIVID-19 ...investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article. Acknowledgement List of participating centres and Co-Investigators TOCIVID-19 Investigators * Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli—Clinical Trials Unit: Francesco Perrone, Maria Carmela Piccirillo, Clorinda Schettino, Adriano Gravina, Piera Gargiulo, Claudia Cardone, Laura Arenare; Melanoma And Cancer Immunotherapy And Developmental Therapeutics Unit: Paolo Antonio Ascierto, Maria Grazia Vitale, Claudia Trojaniello, Marco Palla; Direction: Attilio Antonio Montano Bianchi, Gerardo Botti, Gianfranco De Feo, Leonardo Miscio. * Università degli Studi della Campania Luigi Vanvitelli, Dipartimento di Salute Mentale e Medicina Preventiva; Ciro Gallo, Paolo Chiodini. * IRCCS Policlinico San Donato—Milano: Laurenzia Ferraris, Massimiliano M. Marrocco-Trischitta, Marco Froldi, Lorenzo Menicanti, Maria Teresa Cuppone, Giulia Gobbo, Chiara Baldessari, Vincenzo Valenti, Serenella Castelvecchio, Federica Poli, Francesca Giacomazzi, Rosangela Piccinni, Maria Laura Annnunziata, Andrea Biondi, Cecilia Bussolari, Manuel Mazzoleni, Andrea Giachi, Annalisa Filtz, Arianna Manini, Enrico Poletti, Federico Masserini, Francesco Conforti, Gianfranco Gaudiano, Vittoria Favero, Alice Moroni, Tommaso Viva, Fabiana Fancoli, Davide Ferrari, Dario Niro, Marco Resta, Andrea Ballotta, Marco Dei Poli, Marco Ranucci. * ASST Papa Giovanni XXIII—Bergamo: Diego Ripamonti, Francesca Binda, Alessandra Tebaldi, Giuseppe Gritti, Luisa Pasulo, Leonardo Gaglio, Roberto Del Fabbro, Leonardo Alborghetti. * ASST Monza—Monza: Paolo Bonfanti, Nicola Squillace, Giulia Giustinetti, Paola Columpsi, Marina Cazzaniga, Serena Capici, Luca Sala, Riccardo Di Sciacca, Giacomo Mosca, Maria Rosa Pirozzi. * ASST degli Spedali Civili di Brescia e Università di Brescia—Brescia: Francesco Castelli, Maria Lorenza Muiesan, Franco Franceschini, Aldo Roccaro, Massimo Salvetti, Anna Paini, Luciano Corda, Chiara Ricci, Lina Tomasoni, Paola Nasta, Silvia Lorenzotti, Silvia Odolini, Emanuele Focà, Eugenia Quiros Roldan, Marco Metra, Stefano Magrini, Paolo Borghetti, Nicola Latronico, Simone Piva, Matteo Filippini, Gabriele Tomasoni, Francesco Zuccalà, Sergio Cattaneo, Francesco Scolari, Nicola Bossini, Mario Gaggiotti, Martina Properzi. * Ospedale Santa Maria Goretti—Latina: Miriam Lichtner, Emanuela Del Giudice, Raffaella Marocco, Anna Carraro, Cosmo Del Borgo, Raffaella Marocco, Valeria Belvisi, Tiziana Tieghi, Margherita De Masi, Paola Zuccalà, Paolo Fabietti, Angelo Vetica, Vito Sante Mercurio, Anna Carraro, Laura Fondaco, Blerta Kertusha, Ambrogio Curtolo, Emanuela Del Giudice, Riccardo Lubrano, Maria Gioconda Zotti, Antonella Puorto, Marcello Ciuffreda, Antonella Sarni, Gabriella Monteforte, Domenico Romeo, Emanuela Viola, Carla Damiani, Antonietta Barone, Barbara Mantovani, Daniela Di Sanzo, Vincenzo Gentili, Massimo Carletti, Massimo Aiuti, Andrea Gallo, Piero Giuseppe Meliante, Salvatore Martellucci, Oliviero Riggio, Vincenzo Cardinale, Lorenzo Ridola, Maria Consiglia Bragazzi, Stefania Gioia, Emiliano Valenzi, Camilla Graziosi, Niccolò Bina, Martina Fasolo, Silvano Ricci, Maria Teresa Gioacchini, Antonella Lucci, Luisella Corso, Daniela Tornese, Parni Nijhawan, Francesco Equitani, Carmine Cosentino, Marcello Palladino, Frida Leonetti, Gaetano Leto, Camillo Gnessi, Giuseppe Campagna, Roberto Cesareo, Francesca Marrocco, Giuseppe Straface, Alessandra Mecozzi, Lidia Cerbo, Valentina Isgrò, Sergio Parrocchia, Giuseppe Visconti, Giorgio Casati. * AOU di Parma—Parma: Carlo Calzetti, Alarico Ariani, Lorenzo Donghi. * AOUI di Verona—Verona: Nicola Duccio Salerno, Evelina Tacconelli, Marco Bertoldi, Paolo Cattaneo, Lorenza Lambertenghi, Leonardo Motta, Luca Omega. * Humanitas Gavazzeni—Bergamo: Giovanni Albano. * AORN Dei Colli—Napoli: Roberto Parrella, Fiorentino Fraganza, Luigi Atripaldi, Vincenzo Montesarchio, Francesco Scarano, Annunziata De Rosa, Amalia Buglione, Sabrina Lavoretano, Gianfranco Gaglione, Mario De Marco, Vincenzo Sangiovanni, Francesco Maria Fusco, Rosaria Viglietti, Elio Manzillo, Carolina Rescigno, Raffaella Pisapia, Giulia Plamieri, Alberto Maraolo, Giosuè Calabria, Mario Catalano, Giuseppe Fiorentino, Anna Annunziata, Giorgio Polistina, Pasquale Imitazione, Mariano Mollica, Vincenzo Esposito, Maurizio D’Abraccio, Rodolfo Punzi, Vincenzo Bianco, Costanza Sbreglia. * Azienda Ospedaliera Umberto I—Siracusa: Rosa Fontana Del Vecchio, Alessandro Bordonali, Antonina Franco. * Arcispedale Santa Maria Nuova IRCCS—Reggio Emilia: Carlo Salvarani, Marco Massari, Giovanni Dolci, Pierpaolo Salsi, Matteo Fontana. * ASST di Cremona—Cremona: Giuseppe Virzì, Calderone Ornella, Alfredo Molteni. * Azienda Ospedaliera San Salvatore—Pesaro: Silvia Gennarini, Umberto Gnudi, Maria Anastasia Ricci, Giancarlo Titolo, Giulio Mensi, Pietro Vuotto, Beatrice Gasperini, Mauro Mancini, Zeno Pasquini. * Ospedale Bassini—Cinisello Balsamo: Paolo Spanu, Stefano Clementi, Simona Pierini, Daniela Bokor, Daniela Gori, Morena Ciofetti, Marina Caimi, Laura Bettazzi, Elisabetta Allevi, Silvia Furiani, Chiara Capitanio, Bernardino Mastropasqua, Claudio Fara, Grazia Pulitanò, Jun Sebastian Matsuno, Francesca Della Porta, Viola Dolfini, Nebiat Balei Beyene. * ASST Degli Spedali Civili Di Brescia—Brescia: Michela Bezzi, Mauro Novali. * AOU di Bologna—Bologna: Pierluigi Viale, Sara Tedeschi, Renato Pascale. * Policlinico S. Matteo—Pavia: Raffaele Bruno, Alessandro Di Filippo, Michele Sachs, Tiberio Oggionni, Michele Di Stefano, Caterina Mengoli. * Ospedale di Conegliano—Conegliano: Cesarina Facchini, De Nardo Daniele. * Azienda Ospedaliera San Salvatore—Pesaro: Gabriele Frausini, Luciano Mucci, Silvia Tedesco, Rita Girolimetti, Elena Manfredini, Anna Maria Di Carlo, Emma Espinosa, Donatella Dennetta. * AOU di Parma—Parma: Andrea Ticinesi, Tiziana Meschi, Antonio Nouvenne. * Azienda Ospedaliera Ordine Mauriziano—Torino: Norbiato Claudio, Francesco Vitale, Marta Saracco. * Ospedale Guglielmo Da Saliceto—Piacenza: Mauro Codeluppi, Elisa Fronti, Patrizia Ferrante. * Ospedale di Fermo—Fermo: Giorgio Amadio Nespola. * AOU di Perugia—Perugia: Daniela Francisci, Andrea Tosti. * Casa Sollievo Della Sofferenza—San Giovanni Rotondo: Cristiano Matteo Carbonelli, Antonio Greco, Maria Giulia Tinti. * Fondazione Poliambulanza Istituto Ospedaliero—Brescia: Roberto Stellini, Camilla Appiani, Piera Reghenzi. * Ospedale Morgagni-Pierantoni—Forlì: Venerino Poletti, Claudia Ravaglia. * Ospedale Area Aretina Nord—Arezzo: Danilo Tacconi, Costanza Malcontenti. * AOU “Maggiore della Carità”—Novara: Pier Paolo Sainaghi, Raffaella Landi, Veronica Vassia, Eleonora Rizzi, Mattia Bellan, Antonella Rossati, Luigi Castello * Policlinico Umberto I—Roma: Claudio Maria Mastroianni, Gianluca Russo. * Presidio Ospedaliero di Jesolo—Jesolo: Toffoletto Fabio, Francesco Saverio Serino, Lucio Brollo, Elena Momesso, Maria Luisa Turati. * ASST Santi Paolo e Carlo—Milano: Antonella D'arminio Monforte, Giulia Marchetti. * Ospedale Civile di Guastalla—Guastalla: Fabrizio Boni, Elisabetta Teopompi, Chiara Trenti, Luca Boracchia, Enrica Minelli, Matteo Fontana, Giulia Ghidoni, Anaflorina Matei, Andrea Caruso. * AO Ospedali Riuniti Villa Sofia e Cervello—Palermo: Giuseppe Arcoleo, Gaetana Camarda, Filippo Catalano, Mario Spatafora. * Ospedale Sacra Famiglia, Fatebenefratelli—Erba: Donato Bettega. * AOU Policlinico Tor Vergata—Roma: Massimo Andreoni, Elisabetta Teti, Loredana Sarmati, Andrea Di Lorenzo, Mariagrazia Celeste. * Ospedali Riuniti Padova Sud—Padova: Fabio Baratto, Jacopo Monticelli, Pietro Criveller. * Ospedale San Paolo—Savona: Antonini Andrea, Anselmo, Riccio. * ASST Spedali Civili Di Brescia—Brescia: Maurizio Castellano, Carlo Cappelli, Federica Corvini, Barbara Zanini. * ASST Spedali Civili Di Brescia, Presidio Ospedaliero Gardone—Brescia: Massimo Crippa, Maurizio Ronconi, Raffaella Costa, Silvia Casella, Loretta Brentana. * Ospedale Civile e Ospedale Dell'Angelo—Mestre: Livio Bernardi, Andrea Frascati, Sandro Panese, Fabio Presotto, Lucio Michieletto, Cristina Bernardi. * Ospedale Santa Maria Delle Croci—Ravenna: Maurizio Fusar. * Presidio Ospedaliero di Cesena—Cesena: Vanni Agnoletti, Martina Farina, Russo. * AOU Careggi—Firenze: Federico Lavorini, Roberta Ginanni. * Istituto Nazionale Malattie Infettive INMI L. Spallanzani, IRCCS—Roma: Fabrizio Palmieri, Silvia Mosti. * Casa Di Cura Beato Palazzolo—Bergamo: Angelo Amaglio, Alessandra Cattaneo. * Istituto Clinico S. Ambrogio Spa—Milano: Silvia Cirri, Andrea Montisci, Chiara Gallazzi, Daniele Cosseta, Barabara Baronio, Lorenzo Rampa. * AO Sant’Anna e San Sebastiano—Caserta: Paolo Maggi, Vincenzo Messina. * Arcispedale Santa Maria Nuova IRCCS—Reggio Emilia: Emanuele Alberto Negri, Chiara Trenti. * Ospedale Generale Provinciale—Macerata: Marialma Berlendis, Maria Cecilia Sabatti. * Azienda Ospedaliera S. Maria—Terni: Michele Palumbo. * ASST Ovest Milanese—Milano: Antonino Mazzone, Paola Faggioli. * Ospedale Bellaria—Bologna: Linda Bussini, Giacomo Fornaro, Francesca Volpato. * Ospedale Maria Vittoria—Torino: Daniele Imperiale, Emilpaolo Manno, Enrico Ferreri, Domenico Martelli, Andrea Verhovez, Silvia Giorgis, Luciana Faccio, Rachele Delli Quadri, Cristina Negro. * Ospedale Giovanni Bosco—Torino: Marcella Converso, Francesca Bosco. * ASST Desenzano Del Garda—Gavardo: Silvia Amadasi, Paolo Prandini, Silvia Cocchi. * Azienda ULSS 6—Vicenza: Vinicio Manfrin, Veronica Del Punta. * PO Sant’Elia—Caltanissetta: Giovanni Mazzola, Giuseppe Sportato. * Ospedale Ca’ Foncello—Treviso: Micaela Romagnoli. * Ospedale Infermi—Rimini: Francesco Cristini
Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational ...methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers.
We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER .
We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies.
As the understanding of the tumor microenvironment has deepened, immunotherapy has become a promising strategy for cancer treatment. In contrast to traditional therapies, immunotherapy is more ...precise and induces fewer adverse effects. In this field, some bacteria have attracted increased attention because of their natural ability to preferentially colonize and proliferate inside tumor sites and exert antitumor effects. Moreover, bacterial components may activate innate and adaptive immunity to resist tumor progression. However, the application of bacteria‐based cancer immunotherapy is hampered by potential infection‐associated toxicity and unpredictable behavior in vivo. Owing to modern developments in genetic engineering, bacteria can be modified to weaken their toxicity and enhance their ability to eliminate tumor cells or activate the antitumor immune response. This review summarizes the roles of bacteria in the tumor microenvironment, current strategies for bacterial engineering, and the synergistic efficiency of bacteria with other immunotherapies. In addition, the prospects and challenges of the clinical translation of engineered bacteria are summarized.
In brief, we summarized the role of bacteria in modulating the immune system. Also, representative strategies for the construction of engineered bacteria and synergistic antitumor effects with immunotherapy were demonstrated. Finally, we also focused on the safety of bacteria and effective routes of administration.
Anti-KIR monoclonal antibodies (mAbs) can enhance the antitumor responses of natural killer (NK) cells. We evaluated the safety of the anti-KIR2D mAb lirilumab in patients with various cancers.
...Thirty-seven patients with hematological malignancies (
= 22) or solid tumors (
= 15) were included in the study. Dose escalation (0.015 to 10 mg/kg) was conducted following a 3 + 3 design. Patients were scheduled to receive four cycles of treatment. In a second (extension) phase 17 patients were treated at 0.015 (
= 9) or 3 mg/kg (
= 8).
No dose-limiting toxicity was recorded. The most frequent lirilumab-related adverse events were pruritus (19%), asthenia (16%), fatigue (14%), infusion-related reaction (14%), and headache (11%), mostly mild or moderate. Pharmacokinetics was dose-dependent and linear, with minimal accumulation resulting from the 4-weekly repeated administrations. Full KIR occupancy (>95%) was achieved with all dosages, and the duration of occupancy was dose-related. No significant changes were observed in the number or distribution of lymphocyte subpopulations, nor was any reduction in the distribution of KIR2D-positive NK cells.
This phase 1 trial demonstrated the satisfactory safety profile of lirilumab up to doses that enable full and sustained blockade of KIR.
Bispecific antibodies (bsAbs) are antibodies that bind two distinct epitopes to cancer.. For use in oncology, one bsAb has been approved and 57 bsAbs are in clinical trials, none of which has reached ...phase 3. These bsAbs show great variability in design and mechanism of action. The various designs are often linked to the mechanisms of actions. The majority of bsAbs engage immune cells to destroy tumor cells. However, some bsAbs are also used to deliver payloads to tumors or to block tumor signaling pathways. This review provides insight into the choice of construct for bsAbs, summarizes the clinical development of bsAbs in oncology and identifies subsequent challenges.
PDF
