Cancer immunotherapy articles within Nature Reviews Clinical Oncology

Featured

  • News & Views |

    Advances in cancer immunotherapy have led to clinical trials of immunotherapy-based neoadjuvant treatments for early stage non-small-cell lung cancer. Evidence for priming of the immune system using both preoperative short-course radiotherapy and immunotherapy in this setting has now emerged from a randomized phase II study incorporating pathological and immunological end points.

    • Famke L. Schneiders
    •  & Suresh Senan

  • Review Article |

    Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated malignancy endemic to southern China, southeast Asia and north Africa. The authors of this Review present a comprehensive overview of advances from the past three decades on the pathogenic role of EBV, and the genomic, epigenomic and immune landscape of NPC, which have led to the development of new biomarkers, therapeutic targets and improved treatment approaches for patients with NPC.

    • Kenneth C. W. Wong
    • , Edwin P. Hui
    •  & Anthony T. C. Chan

  • Review Article |

    Immune-checkpoint inhibitors (ICIs) are now standard-of-care therapies for patients with advanced-stage non-small-cell lung cancer (NSCLC) without a targetable driver alteration. Various ICIs or combination regimens have been approved in this setting, relative to chemotherapy, although no prospective data are available comparing the various ICI-based approaches. Here, the authors provide guidance on selecting the optimal ICI-based therapy and highlight several future research directions that will probably further improve the outcomes of patients with advanced-stage NSCLC.

    • Michael J. Grant
    • , Roy S. Herbst
    •  & Sarah B. Goldberg

  • Perspective |

    Patients with primary central nervous system (CNS) malignancies largely do not derive benefit from immune-checkpoint inhibitors. Paradoxically, a subset of those with CNS metastases from tumours located outside of the CNS will respond to the same approach. In this Perspective, the authors explore the key differences in the immune cell composition of primary CNS malignancies and brain metastases and provide guidance on potential alternative immunotherapies that might be effective in patients with these historically difficult-to-treat malignancies.

    • Martina Ott
    • , Robert M. Prins
    •  & Amy B. Heimberger

  • Review Article |

    Limited penetration into tumour tissue can restrict the activity of systemically delivered cancer immunotherapies, whereas exposure of various non-malignant tissues to high levels of such agents can lead to problematic toxicities. Intratumoural administration and/or biotechnology strategies for selective targeting of tumour tissues have the potential to circumvent these issues and thereby increase the therapeutic index. Herein, the authors review the historical origins and current landscape of intratumoural and tumour tissue-targeted immunotherapies.

    • Ignacio Melero
    • , Eduardo Castanon
    •  & Aurelien Marabelle

  • Review Article |

    The authors of this Review present the current considerations in the treatment of patients with early-stage lung cancer, discussing the critical determination of resectability by thoracic surgical oncologists and the management of both resectable and unresectable disease with a focus on systemic therapy selection. They also address innovations in drug development, trial design and efforts to identify early-stage cancers.

    • Jamie E. Chaft
    • , Andreas Rimner
    •  & Tina Cascone

  • Comment |

    Data from several trials support the efficacy of first-line tyrosine-kinase inhibitors combined with immune-checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma. However, whether combining these drugs is preferable to using them sequentially remains unclear. Here, we assess the implications for patients and payers of limited access to second-line ICIs in the control arms of trials.

    • Garth W. Strohbehn
    •  & Daniel A. Goldstein

  • Review Article |

    Despite considerable progress in the development of targeted therapies, only three biomarkers are currently used to guide the treatment of patients with gastric or gastro-oesophageal junction cancers using approved targeted therapies. Nonetheless, owing to advances in our understanding of tumour biology and sequencing technologies, several novel therapies are expected to soon become available. In this Review, the authors describe current and future biomarker-guided therapies for patients with G/GEJ cancers.

    • Yoshiaki Nakamura
    • , Akihito Kawazoe
    •  & Kohei Shitara

  • News & Views |

    An unfavourable gut bacterial composition has been shown to reduce the likelihood of clinical benefit from immune-checkpoint inhibitors (ICIs). The results of two first-in-human studies of faecal microbiota transplantation in patients with melanoma refractory to anti-PD-1 antibodies validate preclinical evidence that this approach can improve the gut microbiota and overcome resistance to ICIs; however, many questions remain.

    • Arielle Elkrief
    •  & Bertrand Routy

  • News & Views |

    A recent meta-analysis examined and validated biomarkers of response to immune-checkpoint inhibitors (ICIs). Herein, we discuss the findings of this analysis, which are consistent with previously identified determinants of ICI efficacy and demonstrate that some genetic variables influence response across multiple cancer types.

    • Tyler J. Alban
    •  & Timothy A. Chan

  • Review Article |

    CD19-specific chimeric antigen (CAR)-modified T cells are approved for patients with advanced-stage forms of certain B cell malignancies. However, a subset of patients will have anti-CAR immune responses, leading to a lack of CAR T cell persistence and a rapid loss of any antitumour efficacy. In this Review, the authors describe the extent of anti-CAR immune responses in patients and suggest measures that could be used to better monitor for these events. Additionally, they describe novel approaches to CAR T cell therapy that might reduce the risk of such responses in the future.

    • Dimitrios L. Wagner
    • , Enrico Fritsche
    •  & Mohamed Abou-el-Enein

  • News & Views |

    The question of whether allogeneic chimeric antigen receptor (CAR) T cells could replace autologous CAR T cell therapy has garnered considerable interest, but limited data have been available for comparisons to date. Now, Benjamin et al. have reported their experience with allogeneic anti-CD19 CAR T cells in 21 paediatric and adult patients with acute lymphoblastic leukaemia.

    • Amanda M. DiNofia
    •  & Stephan A. Grupp

  • Consensus Statement |

    In this Consensus Statement, members from five working groups or societies provide updated comprehensive recommendations to manage toxicities from cancer immunotherapies in children, adolescents and young adults. In their recommendations, they advocate for the adoption of age-based and discipline-specific management criteria, and call for an increased inclusion of young patients with cancer in clinical trials.

    • Dristhi Ragoonanan
    • , Sajad J. Khazal
    •  & Kris M. Mahadeo

  • Review Article |

    PD-L1 expression is currently the best available biomarker for the prediction of responsiveness to immune-checkpoint inhibitors. However, several immunohistochemical assays are now approved for clinical use in various settings, despite imperfect inter-assay concordance, with important implications for pathology services and, potentially, for clinical outcomes. In this Review, the authors compare the performance of the various FDA-approved PD-L1 assays, discuss the varying implications of PD-L1 expression across different tumour types and provide guidance on possible novel approaches that might optimize the clinical utility of PD-L1 as a biomarker.

    • Deborah Blythe Doroshow
    • , Sheena Bhalla
    •  & Fred R. Hirsch

  • Review Article |

    A host of additional toxicities and/or potential late effects of chimeric antigen receptor (CAR) T cell therapy beyond cytokine release syndrome (CRS) warrant further investigation. Herein, experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation present six key focus research areas related to CAR T cell-related outcomes beyond CRS.

    • Haneen Shalabi
    • , Juliane Gust
    •  & Nirali N. Shah

  • Review Article |

    Personalized neoantigen-based therapeutic vaccines hold promise as cancer immunotherapies. This Review provides an overview of the complex personalized neoantigen vaccine production process, vaccine-induced T cell responses and strategies to enhance these responses. Completed and ongoing clinical studies testing such vaccines are discussed, and considerations for future clinical investigation of this novel, individualized form of immunotherapy are outlined.

    • Eryn Blass
    •  & Patrick A. Ott

  • Review Article |

    Renal cell carcinomas (RCCs) are generally immunogenic, but only a subset of patients receiving currently approved immune-checkpoint inhibitors have long-term disease remission. In this Review, the authors provide a conceptual framework for developing novel immunotherapy approaches, including an overview of the most promising novel immune checkpoints and antigen-directed therapies, and highlighting the potential of these agents to further improve the outcomes in patients with RCC.

    • David A. Braun
    • , Ziad Bakouny
    •  & Toni K. Choueiri

  • News & Views |

    Studies have identified multiple molecular properties with a biological rationale supporting a role in mediating selective responses to immune-checkpoint inhibitors (ICIs), including loss-of-function mutations in mSWI/SNF chromatin regulators; however, their clinical biomarker relevance is uncertain. Herein, we evaluate emerging concepts, challenges and considerations around translating biology into biomarkers for ICIs in solid tumours setting.

    • Eliezer M. Van Allen
    •  & Toni K. Choueiri

  • News & Views |

    Tumour-associated antigens are an attractive therapeutic target in immuno-oncology. Here, the exploratory analyses of T cell responses and preliminary clinical outcomes of the Lipo-MERIT trial of a melanoma vaccine are discussed in the context of prior efforts to harness the immunogenicity of such antigens for antitumour immunity.

    • Anjali Rohatgi
    •  & John M. Kirkwood

  • Review Article |

    Despite several major therapeutic advances, multiple myeloma (MM) remains largely incurable, indicating a need for novel therapies. Thus, considerable research interest exists in chimeric antigen receptor (CAR) T cells targeting BCMA, which is almost universally expressed on MM cells. In this Review, the authors describe the clinical experience with anti-BCMA CAR T cells and discuss several new directions of future research that might prolong the responses of patients receiving these therapies.

    • Lekha Mikkilineni
    •  & James N. Kochenderfer

  • Review Article |

    Natural killer (NK) cells have an innate potential to kill cancerous cells and considerable effort is being focused on innovative approaches to leverage these cells for cancer therapy. Herein, the authors discuss the variety of NK cell-based therapies that are being developed for the treatment of diverse cancers and identify future avenues for NK cell therapy research.

    • Jacob A. Myers
    •  & Jeffrey S. Miller

  • Comment |

    Single-arm phase II trials can provide compelling results that facilitate the approval of a new therapy. Designing and interpreting single-arm studies based on four principles — instinct, comparative analysis, statistical soundness and like-for-like comparisons — can provide indications as to which drugs are most likely to provide improved therapeutic options for patients.

    • Robert H. Glassman
    • , Grace Kim
    •  & Marc J. Kahn

  • Review Article |

    The efficacy of chemotherapy in patients with cancer is now known to have an immunogenic component. Nonetheless, chemotherapy alone often fails to provide durable disease remission in most patients. The development of immune checkpoint inhibitors has created an opportunity to combine immunogenic chemotherapies with these agents in order to optimize patient outcomes. In this Review, the authors describe the mechanisms of synergy between chemotherapy and immune checkpoint inhibitors, summarize the available clinical data on these effects and highlight the most promising areas for future research.

    • Lorenzo Galluzzi
    • , Juliette Humeau
    •  & Guido Kroemer

  • Review Article |

    Immune-checkpoint inhibition has transformed the treatment of patients with advanced-stage cancers. Nonetheless, the specific antigens targeted by T cells that are activated or reactivated by these agents remain largely unknown. In this Review, the authors describe the characterization and classification of tumour antigens including descriptions of the most appropriate detection methods, and discuss potential regulatory issues regarding the use of tumour antigen-based therapeutics.

    • Sebastian P. Haen
    • , Markus W. Löffler
    •  & Peter Brossart

  • Review Article |

    Therapies are being developed to treat cancers on the basis of specific molecular alterations and markers of immune phenotypes that transcend specific tumour histologies. The authors summarize the development and testing of approved histology-agnostic therapeutic agents, present data on other agents under development and discuss the challenges intrinsic to histology-agnostic drug development in oncology, including biological, regulatory, design and statistical considerations.

    • Roberto Carmagnani Pestana
    • , Shiraj Sen
    •  & David S. Hong

  • Review Article |

    Signalling induced by extracellular adenosine (eADO) can suppress antitumour immunity through multiple mechanisms. Herein, the authors review the pathophysiological functions of eADO in cancer and the related prognostic implications. They discuss the associated opportunities for eADO pathway-targeted immunotherapy, highlighting potential limitations and the scope for combination and biomarker-based strategies. The data emerging from oncology clinical trials of the diverse range of therapies that have been developed to target the eADO signalling pathway are also described.

    • Bertrand Allard
    • , David Allard
    •  & John Stagg

Browse broader subjects

Browse Cancer immunotherapy across other nature.com journals