Article
Immunology
Ahmet Murat Aydin, MacLean Hall, Brittany L. Bunch, Holly Branthoover, Zachary Sannasardo, Amy Mackay, Matthew Beatty, Amod A. Sarnaik, John E. Mullinax, Philippe E. Spiess, Shari Pilon-Thomas
Summary: This study demonstrated successful expansion of tumor-reactive TIL from penile cancer patients, supporting the development of ACT strategies using TIL for the treatment of advanced and recurrent penile cancer.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Health Care Sciences & Services
Bogdan Marian Caraban, Elena Matei, Georgeta Camelia Cozaru, Mariana Aschie, Mariana Deacu, Manuela Enciu, Gabriela Izabela Baltatescu, Anca Chisoi, Nicolae Dobrin, Lucian Petcu, Emma Gheorghe, Laurentiu-Tony Hangan, Mihai Catalin Rosu, Cristian Ionut Orasanu, Antonela-Anca Nicolau
Summary: This study aimed to characterize the PD-L1 expression in melanomas and its association with T cell infiltrates. The results showed that most of the PD-L1 positive tumors had moderate scores of CD4+ and CD8+ TILs in tumoral melanoma cells. PD-L1 expression was associated with different degrees of lymphocytic infiltration and with Breslow tumor thickness. PD-L1 expression is a predictive biomarker for discriminating the presence or absence of malign tumoral melanoma cells and an independent predictor of good prognosis in melanoma patients.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Review
Oncology
Yueshui Zhao, Jian Deng, Shuangfeng Rao, Sipeng Guo, Jing Shen, Fukuan Du, Xu Wu, Yu Chen, Mingxing Li, Meijuan Chen, Xiaobing Li, Wanping Li, Li Gu, Yuhong Sun, Zhuo Zhang, Qinglian Wen, Zhangang Xiao, Jing Li
Summary: Cell-based immunotherapy, especially tumor-infiltrating lymphocytes (TILs) therapy, has emerged as a powerful strategy in solid cancer treatment. This review summarizes the current strategies and challenges in TIL generation, and discusses the clinical trials where TIL therapy is used independently or in combination with other therapies for solid tumor treatment. The limitations, future potential, and directions of TIL therapy for solid tumors are also discussed.
Article
Oncology
Yunbi Ni, Julia Y. Tsang, Yan Shao, Ivan K. Poon, Fiona Tam, Ka-Ho Shea, Gary M. Tse
Summary: This study investigated the clinicopathological features of breast cancer associated with PD-L1 expression and its relationship with other immune components. The results showed a positive correlation between PD-L1 expression and higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1 expression was also associated with certain receptors and markers. Survival analysis revealed associations between PD-L1 expression and better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in specific subtypes of breast cancer. The combination of PD-L1 expression and tumor-infiltrating lymphocytes (TIL) further refined the prognosis of breast cancer subtypes.
Article
Oncology
Veronica Finisguerra, Tereza Dvorakova, Matteo Formenti, Pierre Van Meerbeeck, Lionel Mignion, Bernard Gallez, Benoit J. van den Eynde
Summary: Despite limitations in certain tumor types and patients, immunotherapies have achieved revolutionary success in cancer treatment. However, the efficacy of immunotherapies is dependent on the viability and functionality of tumor antigen-specific CD8 T cells within the immunosuppressive tumor microenvironment, where oxygen levels are often low. This study reveals that the antidiabetic drug metformin can improve CD8 T cell fitness in hypoxia, increasing their proliferation and cytokine production, and enhancing their infiltration and survival in hypoxic tumor areas. This presents a promising strategy to overcome resistance to immunotherapy in hypoxic and immunosuppressive tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Ahmet Murat Aydin, Brittany L. Bunch, Matthew Beatty, Ali Hajiran, Jasreman Dhillon, Amod A. Sarnaik, Shari Pilon-Thomas, Michael A. Poch
Summary: TIL therapy has shown durable objective responses in patients with metastatic melanoma, with expansion of tumor-reactive TIL being feasible in bladder cancer patients as well. Mixed urothelial carcinoma demonstrates higher anti-tumor reactivity of expanded TIL compared to pure urothelial carcinoma, while prior BCG immunotherapy may reduce the anti-tumor reactivity of expanded TIL from primary tumors. The addition of agonistic 4-1BB antibody in culture media with IL-2 could improve the expansion of TIL from primary tumors previously treated with BCG immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Wei Shi, Mackenzie Fijardo, Jeff P. Bruce, Jie Su, Wei Xu, Rachel Bell, Pierre-Antoine Bissey, Angela B. Y. Hui, John Waldron, Trevor J. Pugh, Kenneth W. Yip, Fei-Fei Liu
Summary: This study reveals the prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in naso-pharyngeal cancer (NPC) and suggests the potential of utilizing CD8+ lymphocytes for immunotherapy.
CLINICAL CANCER RESEARCH
(2022)
Article
Biology
Benedetta De Ponte Conti, Annarita Miluzio, Fabio Grassi, Sergio Abrignani, Stefano Biffo, Sara Ricciardi
Summary: The systematic analysis on translation rate of tumor-infiltrating lymphocytes (TILs) in humans and mice shows that high translation levels are associated with mTORC1 activation and low levels are correlated with hypoxia. CD8 translating cells exhibit a cytotoxic phenotype, while CD4 translating cells are mainly regulatory T cells with immunosuppressive functions.
Article
Immunology
Andrea Aran, Gonzalo Lazaro, Vicente Marco, Elisa Molina, Ferran Abanco, Vicente Peg, Maria Gion, Laia Garrigos, Jose Perez-Garcia, Javier Cortes, Merce Marti
Summary: Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic value in breast cancer. TCR differences between CD4+ and CD8+ TILs were observed, and a more restricted TCR repertoire with higher similarity was found in CD4+ TILs.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Jara Palomero, Carla Panisello, Maria Lozano-Rabella, Ricky Tirtakasuma, Judit Diaz-Gomez, Daniela Grases, Helena Pasamar, Laura Arregui, Eduard Dorca Duch, Esther Guerra Fernandez, Ana Vivancos, Carlos E. de Andrea, Ignacio Melero, Jordi Ponce, August Vidal, Josep Maria Piulats, Xavier Matias-Guiu, Alena Gros
Summary: Our study investigates the prevalence, phenotype, specificity and prognostic value of tumor infiltrating lymphocytes (TILs) in endometrial cancer (EC). We found that CD8(+)TILs expressing high levels of PD-1 and CD39 were associated with tumor reactivity and improved patient survival. The co-expression of inhibitory and activation markers on PD-1(hi) CD4(+) T cells was also observed, which accumulated antitumor T cells and correlated with prolonged survival in EC patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Daniele Borsetto, Michele Tomasoni, Karl Payne, Jerry Polesel, Alberto Deganello, Paolo Bossi, James R. Tysome, Liam Masterson, Giancarlo Tirelli, Margherita Tofanelli, Paolo Boscolo-Rizzo
Summary: This study provides evidence for the prognostic significance of CD8+ and CD4+ TILs in HNSCC, with variations in tumor subsite needing further investigation. TILs may serve as predictive biomarkers for risk stratifying patients and further research is needed in the application of immune-checkpoint inhibitors.
Article
Oncology
Xiaobao Yang, Jinrong Lin, Guanzheng Wang, Dakang Xu
Summary: This study suggests that targeting proliferating tumor-infiltrating macrophages may increase CD8(+) cytotoxic lymphocyte (CTL) infiltration and facilitate the spatial redistribution of CD8(+) T cells in tumors, contributing to the antitumor effect.
Article
Multidisciplinary Sciences
Paulino Tallon de Lara, Hector Castanon, Marijne Vermeer, Nicolas Nunez, Karina Silina, Bettina Sobottka, Joaquin Urdinez, Virginia Cecconi, Hideo Yagita, Farkhondeh Movahedian Attar, Stefanie Hiltbrunner, Isabelle Glarner, Holger Moch, Sonia Tugues, Burkhard Becher, Maries van den Broek
Summary: The study reveals that CD39(+)PD-1(+)CD8(+) T cells play a critical role in dormant metastasis of breast tumors and are associated with dormancy in the lungs.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Fumihiko Kinoshita, Tetsuzo Tagawa, Takaki Akamine, Kazuki Takada, Yuichi Yamada, Yuka Oku, Keisuke Kosai, Yuki Ono, Kensuke Tanaka, Sho Wakasu, Taro Oba, Atsushi Osoegawa, Mototsugu Shimokawa, Yoshinao Oda, Tomoaki Hoshino, Masaki Mori
Summary: High expression of IL-38 in tumor cells is significantly associated with reduced CD8(+)TILs and tumor progression, suggesting IL-38 could be a therapeutic target for lung cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Respiratory System
Galam Leem, Minwoo Jeon, Kun Woo Kim, Seongju Jeong, Seong Jin Choi, Yong Joon Lee, Eui-Soon Kim, Jae-Ik Lee, Seung Yeon Ha, Su-Hyung Park, Hyo Sup Shim, Jin Gu Lee, Shin Myung Kang, Eui-Cheol Shin
Summary: The study found virus-specific bystander CD8(+) TILs in human NSCLC tissues, and demonstrated that IL-15 treatment can activate these TILs to produce IFN-gamma. IL-15 treatment reduced tumor nodules in MCMV-infected mice, suggesting a potential for IL-15 to be repurposed for tumor immunotherapy using bystander CD8(+) TILs.
Review
Oncology
James Isaacs, Aaron C. Tan, Brent A. Hanks, Xiaofei Wang, Kouros Owzar, James E. Herndon, Scott J. Antonia, Steven Piantadosi, Mustafa Khasraw
Summary: This article discusses the application of clinical trials in immuno-oncology, highlighting the importance of primary outcomes based on pharmacokinetic or pharmacodynamic immunologic mechanisms. It also explores the underutilization of these trials and showcases how new technologies and translational approaches can be effectively used in developing different types of immunotherapeutic agents.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Anna Minchom, Aaron C. Tan, Erminia Massarelli, Vivek Subbiah, Valentina Boni, Bruce Robinson, Lori J. Wirth, Lisa M. Hess, Min-Hua Jen, Jennifer Kherani, Elizabeth Olek, Caroline E. McCoach
Summary: This study investigates the patient-reported outcomes of selpercatinib treatment in patients with RET fusion-positive NSCLC, with the majority showing stable or improved health-related quality of life during the treatment period. A significant percentage of patients experienced improvements in dyspnea and pain, suggesting potential therapeutic benefits.
Review
Oncology
Kirit Singh, Kristen A. Batich, Patrick Y. Wen, Aaron C. Tan, Stephen J. Bagley, Michael Lim, Michael Platten, Howard Colman, David M. Ashley, Susan M. Chang, Rifaquat Rahman, Evanthia Galanis, Alireza Mansouri, Vinay K. Puduvalli, David A. Reardon, Solmaz Sahebjam, John H. Sampson, John Simes, Donald A. Berry, Gelareh Zadeh, Tim F. Cloughesy, Minesh P. Mehta, Steven Piantadosi, Michael Weller, Amy B. Heimberger, Mustafa Khasraw
Summary: Immunotherapy has not shown significant improvement in outcomes for glioblastoma patients due to the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Combinatorial approaches of immune-oriented therapy are required to overcome these mechanisms. The design of clinical trials evaluating these approaches needs careful consideration.
CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
Aaron C. Tan, Daniel S. W. Tan
Summary: The therapeutic landscape of non-small-cell lung cancer is undergoing significant changes with the shift from histology-based classification to molecularly defined subsets. Targeted therapies for specific driver mutations such as EGFR, ALK, and ROS1 have shown promising results, and there is a growing list of approved therapies for other mutations. The importance of diagnostic molecular testing, optimal sequencing of therapies, application of targeted therapies in early-stage disease, and the impact of genomic mutations on targeted therapy efficacy are important areas of research.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Yuan Tian, Lindsay N. Carpp, Helen E. R. Miller, Michael Zager, Evan W. Newell, Raphael Gottardo
Summary: This review summarizes existing studies using single-cell technologies to investigate the immune responses and molecular mechanisms in COVID-19. Understanding the immune cell subsets and molecular factors associated with protective or pathological immunity may contribute to the development of vaccines and therapeutics for COVID-19. Single-cell technologies show promise in uncovering the heterogeneity of immune responses and pathogenesis mechanisms of COVID-19.
NATURE BIOTECHNOLOGY
(2022)
Article
Oncology
Stephanie P. L. Saw, Win Pin Ng, Siqin Zhou, Gillianne G. Y. Lai, Aaron C. Tan, Mei -Kim Ang, Wan-Teck Lim, Ravindran Kanesvaran, Quan Sing Ng, Amit Jain, Wan Ling Tan, Tanujaa Rajasekaran, Johan W. K. Chan, Yi Lin Teh, Mengyuan Pang, Jia-Chi Yeo, Angela Takano, Boon-Hean Ong, Eng-Huat Tan, Sze Huey Tan, Anders J. Skanderup, Daniel S. W. Tan
Summary: The aim of this study was to compare the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated and EGFR-wildtype non-small cell lung cancer (NSCLC). The results showed that PD-L1 > 1% was an independent predictor of worse prognosis in EGFR-mutated NSCLC and was associated with inferior disease-free survival (DFS) regardless of EGFR status. Therefore, PD-L1 score should be evaluated as a risk stratification factor in prospective adjuvant studies among EGFR-mutated NSCLC.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Nicholas A. Vitanza, Ashley L. Wilson, Wenjun Huang, Kristy Seidel, Christopher Brown, Joshua A. Gustafson, Jason K. Yokoyama, Adam J. Johnson, Blake A. Baxter, Ryan W. Koning, Aquene N. Reid, Michael Meechan, Matthew C. Biery, Carrie Myers, Stephanie D. Rawlings-Rhea, Catherine M. Albert, Samuel R. Browd, Jason S. Hauptman, Amy Lee, Jeffrey G. Ojemann, Michael E. Berens, Matthew D. Dun, Jessica B. Foster, Erin E. Crotty, Sarah E. S. Leary, Bonnie L. Cole, Francisco A. Perez, Jason N. Wright, Rimas J. Orentas, Tony Chour, Evan W. Newell, Jeffrey R. Whiteaker, Lei Zhao, Amanda G. Paulovich, Navin Pinto, Juliane Gust, Rebecca A. Gardner, Michael C. Jensen, Julie R. Park
Summary: This study reports the first administration of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG, indicating tolerability, detection of CAR T cells in the CSF, elevation of CSF cytokines supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF.
Editorial Material
Oncology
Aaron C. Tan, Keigo Kobayashi, Stephanie P. L. Saw, Daniel S. W. Tan, Darren Wan-Teck Lim
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Keigo Kobayashi, Aaron C. Tan
Summary: The development of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. However, drug resistance remains a challenge in the long-term management of patients. This review highlights the role of intratumoral heterogeneity and drug-tolerant persister (DTP) cells in NSCLC resistance mechanisms. Changes in the tumor microenvironment, chromosomal instability, and extrachromosomal DNA (ecDNA) also contribute to intratumoral heterogeneity and drug resistance. Comprehensive genomic profiling has provided valuable insights into primary resistance mechanisms in the context of tumor heterogeneity. Understanding these mechanisms is crucial for developing individualized anticancer therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Celestine N. Wanjalla, Curtis L. Gabriel, Hubaida Fuseini, Samuel S. Bailin, Mona Mashayekhi, Joshua Simmons, Christopher M. Warren, David R. Glass, Jared Oakes, Rama Gangula, Erin Wilfong, Stephen Priest, Tecla Temu, Evan W. Newell, Suman Pakala, Spyros A. Kalams, Sara Gianella, David Smith, David G. Harrison, Simon A. Mallal, John R. Koethe
Summary: People with HIV on long-term antiretroviral therapy have a higher risk of cardiometabolic diseases, partly due to persistent inflammation despite viral suppression. Immune responses to co-infections, such as cytomegalovirus, may contribute to these comorbidities and could be targeted for potential therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Oncology
Tony Chour, Alexandre Hirayama, Ye Zheng, Alyssa Sheih, Summer Zhuang, Ashley Wilson, Vicky Wu, Raphael Gottardo, Cameron Turtle, Rebecca Gardner, Evan Newell
Article
Medicine, Research & Experimental
Shigeki Nanjo, Wei Wu, Niki Karachaliou, Collin M. Blakely, Junji Suzuki, Yu-Ting Chou, Siraj M. Ali, D. Lucas Kerr, Victor R. Olivas, Jonathan Shue, Julia Rotow, Manasi K. Mayekar, Franziska Haderk, Nilanjana Chatterjee, Anatoly Urisman, Jia Chi Yeo, Anders J. Skanderup, Aaron C. Tan, Wai Leong Tam, Oscar Arrieta, Kazuyoshi Hosomichi, Akihiro Nishiyama, Seiji Yano, Yuriy Kirichok, Daniel S. W. Tan, Rafael Rosell, Ross A. Okimoto, Trever G. Bivona
Summary: This study investigates the impact of co-occurring genetic alterations on mutant EGFR and identifies the deficiency of RNA-binding factor RBM10 as a factor that decreases the efficacy of EGFR inhibitors in lung cancer treatment. The study reveals that RBM10 modulates tumor cell apoptosis by regulating the alternative splicing of Bcl-x and its deficiency diminishes EGFR inhibitor-mediated apoptosis. The findings suggest that co-occurring genetic alterations and splicing factor deficiency play a role in determining the sensitivity to targeted kinase inhibitor therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Oncology
Mahesh Yadav, Michael Fehlings, Leesun Kim, Xiangnan Guan, Kobe C. Yuen, Alireza Tafazzol, Deepali Rishipathak, Shomyesh Sanjabi, Andrew Wallace, Alessandra Nardin, Siming Ma, Ana Milojkovic, Evan Newell, Sanjeev Mariathasan
Meeting Abstract
Oncology
Evan W. Newell