Data Availability Sample metadata file are available from GitLab (https://gitlab.com/cruk-mi/tcell-immune-awakening). The data from all TCR sequencing performed for this study are deposited in ImmunoSEQ® Immune ACCESS repository (https://clients.adaptivebiotech.com/ immuneaccess). The RNA-Seq data for patient #12 can be downloaded from EGA (accession code EGAS00001004043). TCR sequencing data for matched pre-treatment and week 3 melanoma biopsy and PBMC samples of locally-advanced melanoma patients 18 re-analyzed here were downloaded from referenced accession EGAS00001003178 EGA study accession dataset EGAD00010001608. TCR sequencing data of matched pre-treatment and week 3 melanoma patient PBMC from AC Huang et al. 7 reanalyzed here were kindly made available by the Authors. TCR sequencing data of matched pre-treatment and week 3 PBMC for the cohort of locally-advanced treatment naive melanoma patients from referenced accession Amaria et al. 18 re-analyzed here were downloaded from EGAS00001003178 EGA study accession dataset EGAD00010001608, patient clinical history metadata file from EGAD00001004352. PBMC and biopsy CyTOF data from Krieg et al. 8 and Greenplate et al. 24 re-analyzed here were downloaded from referenced accession https://flowrepository.org/experiments/1124 and http://flowrepository.org/id/FR-FCM-ZZMC, respectively. PBMC REAP-Seq data from Peterson et al. 27 re-analyzed here were downloaded from referenced accession https:// www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100501. The authors confirm that, for approved reasons (UK Data Protection Act 2018), some access restrictions apply to data containing patient medical records (date of birth). Source data for Fig. 1-7 and Extended Data Fig. 3-6 are provided as Source Data files Fig. 1-7 and Extended Data Fig. 3-6. Additional data that support the findings of this study are available from the corresponding author on reasonable request.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by mutation/deletion of the NF1 gene. The gene product, neurofibromin, is a tumor suppressor which represses the activity of the Ras oncogene. Central nervous system (CNS) tumors have long been associated with NF1, but their association with several other malignancies has been demonstrated. In this review, we summarize the epidemiological data that irrefutably support a link between NF1 and an increased risk of early-onset breast cancer, to levels at which annual mammography is currently recommended in national high-risk screening programs. We discuss the reasons for the observed adverse breast cancer prognosis in NF1 cases, including late presentation and more aggressive tumor subtypes, and recommend that a collaborative breast screening study be initiated to better serve this currently underserved population of women.

Small cell lung cancer (SCLC) is a very aggressive disease, characterised by rapid growth, high response rates to both chemotherapy and radiotherapy and subsequent development of treatment resistance in the vast majority of patients. In the past 30 years, little progress has been made in systemic treatments and the established management paradigm of platinum-based chemotherapy has reached an efficacy plateau. Several clinical trials have investigated targeted therapies, without producing clinically significant benefits. Recently presented early phase clinical trials with immune checkpoint inhibitors (blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) and blockade of the programmed cell death-1 (PD-1) receptor) have shown promising results. In this review, we present the emerging evidence on immune checkpoint blockade for SCLC.

Purpose: Taxane chemotherapy is commonly used in the management of breast cancer. Hair loss (alopecia) is an expected side effect which may have a significant effect on quality of life. Alopecia is normally temporary but permanent chemotherapy-induced alopecia (pCIA) is increasingly recognised especially following docetaxel chemotherapy. However, the prevalence following docetaxel is not well understood and there is no published literature for paclitaxel chemotherapy. The aim of this study is to investigate the prevalence and patterns of pCIA resulting from both docetaxel and paclitaxel chemotherapy at two tertiary UK cancer centres. Methods: In collaboration between Clatterbridge Cancer Centre and The Christie NHS Foundation Trusts, a retrospective survey was conducted for breast cancer patients who had received taxane chemotherapy in the neoadjuvant and adjuvant settings. Patients who had concluded chemotherapy at least a year previously were contacted by post and invited to participate by completing a questionnaire and returning it to their treatment centre. Data collected included the incidence and pattern of pCIA using the Savin pictorial hair loss scale, and the methods used by patients to manage it. Fisher's exact test was used to compare pCIA between the docetaxel and paclitaxel cohorts.Results: 383 patients responded to the survey (a 63.3% overall response rate). These comprised 245 patients receiving docetaxel and 138 patients treated with paclitaxel.pCIA was reported by 23.3% of patients receiving docetaxel and 10.1% paclitaxel (p < 0.01). Overall 16.7% of patients in both groups reported the ongoing use of products or appliances such as wigs to camouflage their pCIA. In the docetaxel group, pCIA appeared to be more frequent in post-menopausal women than peri-or premenopausal women (37.8%, 12.3% and 19.6% respectively [Chi-square test p < 0.01]).Also in the docetaxel group, there appeared to be a trend for more severe scalp alopecia when the patient also received an aromatase inhibitor (AI) or tamoxifen and this difference was most marked in those who had received both an AI and tamoxifen as components of their treatment regime (p = 0.04). The use of scalp cooling was How to cite this article: Chan J, Adderley H, Alameddine M, et al. Permanent hair loss associated with taxane chemotherapy use in breast cancer: A retrospective survey at two tertiary UK cancer centres. Eur J Cancer Care.

Background:Histopathological prognostication relies on morphological pattern recognition, but as numbers of biomarkers increase, human prognostic pattern-recognition ability decreases. Follicular lymphoma (FL) has a variable outcome, partly determined by FOXP3 Tregs. We have developed an automated method, hypothesised interaction distribution (HID) analysis, to analyse spatial patterns of multiple biomarkers which we have applied to tumour-infiltrating lymphocytes in FL.Methods:A tissue microarray of 40 patient samples was used in triplex immunohistochemistry for FOXP3, CD3 and CD69, and multispectral imaging used to determine the numbers and locations of CD3+, FOXP3/CD3+ and CD69/CD3+ T cells. HID analysis was used to identify associations between cellular pattern and outcome.Results:Higher numbers of CD3+ (P=0.0001), FOXP3/CD3+ (P=0.0031) and CD69/CD3+ (P=0.0006) cells were favourable. Cross-validated HID analysis of cell pattern identified patient subgroups with statistically significantly different survival (35.5 vs 142 months, P=0.00255), a more diffuse pattern associated with favourable outcome and an aggregated pattern with unfavourable outcome.Conclusions:A diffuse pattern of FOXP3 and CD69 positivity was favourable, demonstrating ability of HID analysis to automatically identify prognostic cellular patterns. It is applicable to large numbers of biomarkers, representing an unsupervised, automated method for identification of undiscovered prognostic cellular patterns in cancer tissue samples.