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While immune checkpoint inhibitors (ICIs) have ushered in major changes in standards of care for many solid tumor malignancies, primary and acquired resistance is common. Insufficient antitumor T cells, inadequate function of these cells, and impaired formation of memory T cells all contribute to resistance mechanisms to ICI. Adoptive cellular therapy (ACT) is a form of immunotherapy that is rapidly growing in clinical investigation and has the potential to overcome these limitations by its ability to augment the number, specificity, and reactivity of T cells against tumor tissue. ACT has revolutionized the treatment of hematologic malignancies, though the use of ACT in solid tumor malignancies is still in its early stages. There are currently three major modalities of ACT: tumor-infiltrating lymphocytes (TILs), genetically engineered T-cell receptors (TCRs), and chimeric antigen receptor (CAR) T cells. TIL therapy involves expansion of a heterogeneous population of endogenous T cells found in a harvested tumor, while TCRs and CAR T cells involve expansion of a genetically engineered T-cell directed toward specific antigen targets. In this review, we explore the potential of ACT as a treatment modality against solid tumors, discuss their advantages and limitations against solid tumor malignancies, discuss the promising therapies under active investigation, and examine future directions for this rapidly growing field.

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer arising in the head and neck region. The most common risk factors are smoking, excessive drinking, and human papillomavirus (HPV) infection. While the overall incidence of smoking is decreasing, the incidence of HPV-related HNSCC is increasing in the United States and Western Europe, which led to a shift in understanding of the pathophysiology, treatment, and prognosis of this disease. The outcomes for non-metastatic HNSCC remains very encouraging and continues to improve. Advances in radiation technology and techniques, better organ preserving surgical options, and multidisciplinary treatment modalities have improved cure rates for locally advanced HNSCC patients. The treatment of metastatic disease, however, remains an area of need. The advancement of immune checkpoint inhibitors has provided significantly better outcomes, but only a small proportion of patients obtain benefits. Most recurrent and/or metastatic HNSCC patients continue to have poor survival. This has led to the vigorous investigation of new biomarkers and biomarker-based therapies. Novel therapeutic options including adaptive cellular therapy and therapeutic vaccines are also on the horizon. In this review, we highlight the latest advances in the field of HNSCC and the future direction of research.

Survivors of head and neck cancer have complex nutritional and supportive care needs. These needs result from the tumour's proximity to organs essential for normal eating function and the intensive treatment targeting those organs. Despite the crucial role of nutrition and supportive care in head and neck cancer, research and funding are lacking compared with other cancer types. This Review was compiled and written by a team of multidisciplinary medical professionals. Topics include poor access to medical nutrition therapy (MNT), MNT reimbursement policies, long-term survivorship care needs, percutaneous endoscopic gastrostomy tube placement, nutrition literacy, psychological services, speech–language pathology care, and concomitant physical activity. The goal of this work is to define current issues in research and practice, advocate for the expansion of head and neck cancer funding opportunities, and raise awareness of head and neck cancer supportive care needs and challenges. This work provides a roadmap for health-care professionals, researchers, policy makers, and funding agencies to prioritise nutrition in head and neck cancer care, with the overarching goal of improving treatment outcomes and quality of life.

Purpose The COVID-19 pandemic has drastically changed cancer care delivery strategies. Patients with locally advanced head and neck cancer (LA-HNC) may be particularly affected by the COVID-19 pandemic, as they often undergo treatments that require daily clinic visits (e.g., radiation therapy). The goal of this study was to characterize the lived experience of LA-HNC patients and their healthcare providers during the COVID-19 pandemic. Methods LA-HNC patients who completed a full course of chemotherapy and radiation therapy during the COVID19 pandemic ( N  = 20) and LA-HNC healthcare providers ( N  = 13) participated in semi-structured interviews. Interviews were audio-recorded, transcribed verbatim, and analyzed for qualitative themes. Results The COVID-19 pandemic had a significant impact on patients’ overall quality of life and health care. Results were organized in four main themes: (1) increased psychological distress; (2) exacerbated social isolation; (3) added stress in clinic for patients and providers; and (4) delays in health care. Conclusions Findings highlight myriad ways LA-HNC patients and providers have been affected by the COVID-19 pandemic. Results can inform the development of supportive interventions to assist LA-HNC in managing COVID-19-related stress and unmet needs related to social isolation and in-clinic support.

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4 + T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4 + T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.

Anemia is prevalent globally and often treated with intravenous (IV) iron formulations, including iron sucrose, iron dextran, ferric carboxymaltose, ferric derisomaltose, and ferumoxytol. IV iron has a high efficacy and safety profile, quickly improving hemoglobin levels with low rates of adverse events. In this work, we report an uncommon case of a cutaneous hypersensitivity reaction following IV iron. A review of the literature shows that acute and delayed cutaneous reactions are possible but rare and respond well to management. Patients should be educated, and staff should be vigilant as to these cutaneous reactions. Clinical Trial Registration:The authors have confirmed that clinical trial registration is not needed for this submission.

BackgroundT cell receptor (TCR) signaling profile is a fundamental property that underpins both adaptive and innate immunity in the host. Despite its potential clinical relevance, the TCR repertoire in peripheral blood has not been thoroughly explored for its value as an immunotherapy efficacy biomarker in head and neck squamous cell carcinoma (HNSCC). The purpose of the present study is to characterize and compare the TCR repertoire in peripheral blood mononuclear cells (PBMC) from patients with HNSCC treated with the combination of cetuximab and nivolumab.MethodsWe used the immunoSEQ assay to sequence the TCR beta (TCR-B) chain repertoire from serially obtained PBMC at baseline and during the treatments from a total of 41 patients who received the combination (NCT03370276). Key TCR repertoire metrics, including diversity and clonality, were calculated and compared between patients with different therapy responses and clinical characteristics (eg, human papillomavirus (HPV) status and smoking history). Patient survival outcomes were compared according to patient groups stratified by the TCR-B clonotyping. To confirm the observed patterns in TCR spectrum, samples from patients who achieved complete response (CR) and partial response (PR) were further profiled with the immunoSEQ deep resolution assay.ResultsOur data indicated that the patients who achieved CR and PR had an increased TCR sequence diversity in their baseline samples, this tendency being more pronounced in HPV-negative patients or those with a smoking history. Notably, the CR/PR group had the lowest proportion of patients with oligoclonal TCR clones (2 out of 8 patients), followed by the stable disease group (9 out of 20 patients) and lastly the progressive disease group (7 out of 10 patients). An overall trend toward favorable patient survival was also observed in the polyclonal group. Finally, we reported the shared TCR clones across patients within the same response group, as well as the shared clones by aligning immunoSEQ reads with TCR data retrieved from The Cancer Genome Atlas- head and neck squamous cell carcinoma (TCGA-HNSC) cohort.ConclusionsOur data suggest that, despite the great clinical heterogeneity of HNSCC and the limited responders in the present cohort, the peripheral TCR repertoires from pretreatment PBMC may be developed as biomarkers for the benefit of immunotherapy in HNSCC.

ObjectiveIdentifying eligible patients for precision oncology clinical trials is challenging, particularly for rare molecular subpopulations. To address this challenge, A2 Biotherapeutics developed BASECAMP-1 (NCT04981119), a non-interventional master screening study to identify patients eligible for interventional studies of logic-gated Tmod chimeric antigen receptor T-cell therapies. Eligible patients for these interventional trials have an advanced solid malignancy and are germline human leucocyte antigen (HLA)-A*02 heterozygous, with tumour-associated HLA-A loss of heterozygosity (LOH). HLA-A LOH occurs in ~16% of advanced solid malignancies; therefore, an efficient screening strategy is required. This report describes BASECAMP-1; compares the efficiency of two screening methods; and discusses the broader advantages of BASECAMP-1 beyond efficient enrolment.Methods and analysisPatients are identified for BASECAMP-1 using two approaches. In the traditional approach, common for clinical trials, investigators consent and screen all patients who might be good candidates for cell therapy trials, with no prior knowledge of patient HLA-A type or LOH status. To further optimise our approach, we co-developed with Tempus AI (Tempus) the bioinformatic programme Aware, which identifies potentially eligible patients with tumour-associated HLA-A*02 LOH within a clinico-genomic database that includes linked genomic and transcriptomic sequencing and clinical data collected during routine care.ResultsOver 42 months of using a traditional approach to identify eligible patients, 1918 patients at 13 study sites were consented and screened for BASECAMP-1; of these, 30 patients with tumour-associated HLA-A*02 LOH were enrolled (~0.7 participants per month). Over the last 30 months of that same period, Tempus Aware screening was implemented and 55 patients with tumour-associated HLA-A*02 LOH were enrolled (~1.8 participants per month). The bioinformatic approach identified more patients than the traditional approach and used sequencing results produced as part of the standard clinical tumour sequencing workflow, reducing resource use and study staff burden. Additional advantages of using a screening study, such as BASECAMP-1, include manufacturing efficiencies and collection of a large dataset of molecular and clinical parameters that can be used to supplement trial analyses.ConclusionsThe BASECAMP-1 study demonstrates a clinico-genomic screening approach can more efficiently identify patients for precision oncology trials. Furthermore, precision oncology can be enhanced through collaborative data-sharing.Trial registration numberNCT04981119.

Background National Cancer Institute cancer centers (NCICCs) provide specialized cancer care including precision oncology and clinical treatment trials. While these centers can offer novel therapeutic options, less is known about when patients access these centers or at what timepoint in their disease course they receive specialized care. This is especially important since precision diagnostics and receipt of the optimal therapy upfront can impact patient outcomes and previous research suggests that access to these centers may vary by demographic characteristics. Here, we examine the timing of patients' presentation at Moffitt Cancer Center (MCC) relative to their initial diagnosis across several demographic characteristics. Methods A retrospective cohort study was conducted among patients who presented to MCC with breast, colon, lung, melanoma, and prostate cancers between December 2008 and April 2020. Patient demographic and clinical characteristics were obtained from the Moffitt Cancer Registry. The association between patient characteristics and the timing of patient presentation to MCC relative to the patient's cancer diagnosis was examined using logistic regression. Results Black patients (median days = 510) had a longer time between diagnosis and presentation to MCC compared to Whites (median days = 368). Black patients were also more likely to have received their initial cancer care outside of MCC compared to White patients (odds ratio [OR] and 95% confidence interval [CI] = 1.45 [1.32–1.60]). Furthermore, Hispanics were more likely to present to MCC at an advanced stage compared to non‐Hispanic patients (OR [95% CI] = 1.28 [1.05–1.55]). Conclusions We observed racial and ethnic differences in timing of receipt of care at MCC. Future studies should aim to identify contributing factors for the development of novel mitigation strategies and assess whether timing differences in referral to an NCICC correlate with long‐term patient outcomes. There are racial differences in timing of receipt of care at our NCI cancer center. Black patients were more likely to have initial care outside of our center, while Hispanic patients were more likely to present with advanced stage.

To enable interrogation of tumor HLA LOH as a clinical diagnostic for precision oncology, we developed and validated an assay that detects HLA LOH within the context of an FDA-approved clinical diagnostic test, Tempus xT CDx. Validation was conducted via: (1) analytical evaluation of 17 archival patient samples and 42 cell line admixtures and (2) independent clinical evaluation of LOH prevalence in the HLA-A gene ( HLA-A LOH) across 10,982 patients. To evaluate the prognostic relevance of HLA-A LOH we assessed 256 immunotherapy-treated non-small cell lung cancer (NSCLC) patients. To determine the feasibility of prospectively identifying and enrolling HLA-A LOH patients into a clinical trial, we established BASECAMP-1 (NCT04981119). We observed a positive predictive agreement of 97% and a negative predictive agreement of 100% in samples with ≥ 40% tumor purity. We observed HLA-A LOH in 16.1% of patients (1771/10,982), comparable to previous reports. HLA-A LOH was associated with longer survival among NSCLC adenocarcinoma patients (HR = 0.60, 95% CI [0.37, 0.96], p  = 0.032) with a trend towards shorter survival among squamous cell patients (HR = 1.64, 95% CI [0.80, 3.41], p  = 0.183). In 20 months, we prospectively screened 1720 subjects using the Tempus AWARE program, identifying 26 HLA-A*02 LOH patients at 8 sites, with 14 (54%) enrolled into BASECAMP-1. In conclusion, we developed and validated an investigational assay that detects tumor HLA LOH within an FDA-approved clinical diagnostic test, enabling HLA LOH utilization in diagnostic, prognostic, and therapeutic applications.