Common inherited loss-of-function mutations in the innate sensor NOD2 contribute to exceptional immune response to cancer immunotherapy.

Lung cancers and melanomas have many somatically mutated self-proteins that would be expected to trigger an immune rejection response, yet therapeutic responses can only be induced in a subset of patients. Here, we investigated the possibility that inherited differences in immune tolerance checkpoints contribute to variability in outcomes. Whole genome sequencing revealed biallelic germline loss-of-function (LOF) mutations in the immune tolerance checkpoint gene, , in an exceptional immune responder to targeted radiotherapy for metastatic melanoma.

Oligometastatic colorectal adenocarcinoma to the spleen and ovaries.

In the context of colorectal cancer, splenic and ovarian metastases are rare outside of widely disseminated disease. Growing evidence suggests that 'oligometastatic' or limited metastatic disease can be treated surgically with good oncological outcomes. Splenic and ovarian metastases are not well represented in studies of oligometastatic colorectal cancer, resulting in uncertainty in the best management for these patients.

Rate of cancer progression as a predictive marker of efficacy of immunotherapy; an analysis in metastatic non-small-cell lung cancer.

To explore the value of rate of cancer progression (ROP) prior to starting PD-1 inhibitors as a predictive and prognostic biomarker. Retrospective data of patients with metastatic non-small-cell lung cancer treated with second-line PD-1 inhibitors were collected. Patients were divided into two groups: slow and rapid based on their ROP.

Immunotherapy in Non-Small Cell Lung Cancer: Shifting Prognostic Paradigms.

Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the immunogenic nature of NSCLC and invigorated research into immunotherapy in the field.

Understanding Immune Tolerance of Cancer: Re-Purposing Insights from Fetal Allografts and Microbes.

Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations.

"Standard Care" in Cancer Clinical Trials: An Analysis of Care Provided to Women in the Control Arms of Breast Cancer Clinical Trials.

For trials to validly evaluate new treatments, comparison against the best existing alternative treatment is essential. We reviewed the care provided to women in control arms of breast cancer clinical trials to estimate the proportion consistent with the standard of care as defined in clinical guidelines. We analyzed phase III randomized controlled breast cancer trials comparing drug treatments with "standard care," enrolling between 2004 and 2014, and registered on ClinicalTrials.

EGFR-Co-Mutated Advanced NSCLC and Response to EGFR Tyrosine Kinase Inhibitors.

Objectives: The evolution of EGFR tyrosine kinase inhibitors (TKIs) has changed the landscape of disease for a subset of patients with NSCLC. Most patients with an EGFR mutation respond to these drugs; however, a proportion show limited or no tumor response. We explored the impact of co-mutation (double or multiple mutation), compared with a single mutation, of the EGFR gene on response to TKIs in a series of patients with metastatic NSCLC.