News & Views

Efforts are being made to incorporate immune-checkpoint inhibitors into therapy for early stage non-small-cell lung cancer. The IMpower010 trial of adjuvant atezolizumab has recently become the first study to demonstrate that this strategy can improve disease-free survival in a subset of patients. This trial opens a new area of research in the quest for the optimal perioperative strategy to increase overall survival.

Chimeric antigen receptor (CAR) T cells have remarkable efficacy in patients with B cell acute lymphoblastic leukaemia (ALL), but have not been successful to date in patients with T cell ALL (T-ALL). Now, data from Pan and colleagues demonstrate the safety and impressive short-term efficacy of allogeneic donor-derived anti-CD7 CAR T cells in an early-phase clinical trial involving patients with relapsed and/or refractory T-ALL.

Two recent studies addressed the functional properties and clinical significance of tumour antigen-specific effector T cells in human melanomas and lung carcinomas using single-cell strategies. Herein, we discuss their findings, which expand our understanding of T cell alterations in the tumour microenvironment and demonstrate that CD8⁺ T cell exhaustion is mediated by exposure to tumour cell-specific antigens and is associated with a tissue-resident memory phenotype.

The paradigm of precision medicine implies that breast cancer treatment should be tailored based on inherent risk of recurrence and/or individual sensitivity to various chemotherapies. A recent trial of olaparib in women with a BRCA1/2 mutation provides supporting evidence for this paradigm and suggests that the identification of genetic variants at the time of diagnosis might benefit an increasing number of patients.

Artificial intelligence and machine learning have the potential to make cancer care more accessible, efficient, cost-effective and personalized. However, meticulously planned prospective deployment strategies are required to validate the performance of these technologies in real-world clinical settings and overcome the human trust barrier.

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.

Whole-genome sequencing of samples from patients with myeloid malignancies can enable more accurate risk stratification than is possible with conventional cytogenetics. Research by Duncavage et al. demonstrates that such an approach can now be delivered within several days using a highly streamlined and automated workflow.

The Kerala Oral Cancer Screening Trial did not demonstrate an overall cancer-related mortality benefit. Herein, we discuss the important lessons learnt from a recent reanalysis of data from this trial in an attempt to demonstrate the advantages of using a novel risk-based approach to cancer screening.

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.

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.

ATM, BRCA1, BRCA2, CHEK2, PALB2 and TP53 are all established breast cancer susceptibility genes. Over the past 30 years, many other genes have been proposed as candidates. In these two large studies, the candidacy of several questionable genes has been largely resolved, and a final list of ten genes for breast and, importantly, ovarian cancer risk has emerged.

Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of patients with recurrent melanoma. Now, a recent study in patients with primary cutaneous B cell lymphoma confirms prior results in melanoma and reveals new mechanisms of action. Herein, we discuss these findings and their implications for expanding the role of oncolytic viruses.

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.

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.

The much anticipated results from two phase III studies evaluating the clinical efficacy of poly(ADP-ribose) polymerase (PARP) inhibition in patients with advanced-stage breast cancer harbouring a germline mutation in BRCA1/2 have established new therapeutic opportunities and yet, have left us with several ongoing questions.

Opposing results of the monarchE and PALLAS trials investigating the role of adjuvant treatment with the CDK4/6 inhibitors abemaciclib and palbociclib, respectively, in patients with hormone receptor-positive, HER2-negative early stage breast cancer have recently been presented. Herein, potential reasons why these two drugs that have similar efficacy in the metastatic setting have produced disparate results in the adjuvant setting are discussed.

Noninvasive liquid biopsy assays integrating tumour and immune biomarkers are a promising tool to enhance clinical decision-making in immuno-oncology. Here, we discuss how circulating tumour DNA dynamics, in conjunction with pre-treatment tumour and immune features, can predict clinical response to immune-checkpoint inhibitors alongside the challenges in making their use a clinical reality.

Randomized controlled trials designed to test cancer therapies often fail to clarify effectiveness in real-world settings. Herein, we explore lessons for trial development in oncology that can be learnt from the large-cohort, pragmatic RECOVERY trial involving patients hospitalized with COVID-19.

We argue that the evidence remains insufficient for use of intraoperative radiotherapy (IORT) in women with early stage breast cancer outside of a clinical trial, as the recently reported TARGIT-A trial does not provide sufficient evidence to conclude that IORT is superior to no radiotherapy.

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.