Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee.

Therapies targeting the programmed cell death protein-1/programmed death-ligand 1 (PD-L1) (abbreviated as PD-(L)1) axis are a significant advancement in the treatment of many tumor types. However, many patients receiving these agents fail to respond or have an initial response followed by cancer progression. For these patients, while subsequent immunotherapies that either target a different axis of immune biology or non-immune combination therapies are reasonable treatment options, the lack of predictive biomarkers to follow-on agents is impeding progress in the field. This review summarizes the current knowledge of mechanisms driving resistance to PD-(L)1 therapies, the state of biomarker development along this axis, and inherent challenges in future biomarker development for these immunotherapies. Innovation in the development and application of novel biomarkers and patient selection strategies for PD-(L)1 agents is required to accelerate the delivery of effective treatments to the patients most likely to respond.

Communication Public Health: An Integration of Audiology, Speech-Language Pathology, and Public Health.

PURPOSE: Health care is advancing toward a collaborative and integrative approach that promotes general health and wellness while addressing health inequities through the consideration of broader social and economic factors that influence the well-being of the entire population. Recently, there has been growing evidence of public health concept applications in fields related to speech, language, and hearing. However, there is an outstanding need to explicitly define the intersection of public health, including prevention and health promotion, and the discipline of communication sciences and disorders (CSD) across the areas of education, clinical practice, research, and policy. The authors propose a definition for this intersection using the new term communication public health. METHOD: This tutorial provides guidance on how to conceptualize communication public health and invites refinement and expansion of the intersection between public health and CSD. Because readers are experts in CSD, this tutorial aims to supplement existing knowledge with information on public health to achieve three main objectives: (a) increase knowledge of the application of public health concepts among speech, language, hearing, and related professionals (SLHP+); (b) introduce the concept of communication public health; and (c) discuss the relevance of communication public health across domains within CSD. The authors utilize the socioecological model to provide examples of applications. RESULTS: The concept of communication public health is proposed as the collaborative area of CSD and public health, which encompasses prevention and promotion of equity in communication health through individual-, community-, and population-level efforts. The goals of communication public health are achieved through applications of public health principles in CSD education, clinical practice, research, and policy. CONCLUSION: Communication public health defines an area of collaboration between public health and CSD in which SLHP+ can apply public health concepts to both advance communication health and address health disparities.

Tumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer.

BACKGROUND: Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA11a linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response. METHODS: Methods involved RNA-SEQ on NSCLC cells with depleted hMENA isoforms. A retrospective observational study assessed tissues from surgically treated N0 patients with NSCLC, using immunohistochemistry for tumoral and stromal hMENA isoforms, fibronectin, and TLS presence. ICB-treated patient tumors were analyzed using Nanostring nCounter and GeoMx spatial transcriptomics. Multiparametric flow cytometry characterized B cells and tissue-resident memory T cells (TRM). Survival and ICB response were estimated in the cohort and validated using bioinformatics pipelines in different datasets. FINDINGS: Findings indicate that hMENA11a in NSCLC cells upregulates the TLS regulator LTßR, decreases fibronectin, and favors CXCL13 production by TRM. Conversely, hMENAΔv6 in CAFs inhibits LTßR-related NF-kB pathway, reduces CXCL13 secretion, and promotes fibronectin production. These patterns are validated in N0 NSCLC tumors, where hMENA11ahigh expression, CAF hMENAΔv6low, and stromal fibronectinlow are associated with intratumoral TLS, linked to memory B cells and predictive of longer survival. The hMENA isoform pattern, fibronectin, and LTßR expression broadly predict ICB response in tumors where TLS indicates an anti-tumor immune response. INTERPRETATION: This study uncovers hMENA alternative splicing as an unexplored contributor to TLS-related Tumor Immune Microenvironment (TIME) and a promising biomarker for clinical outcomes and likely ICB responsiveness in N0 patients with NSCLC. FUNDING: This work is supported by AIRC (IG 19822), ACC (RCR-2019-23669120), CAL.HUB.RIA Ministero Salute PNRR-POS T4, "Ricerca Corrente" granted by the Italian Ministry of Health.

Audiologists' attitudes and practice toward referring for psychosocial intervention with cochlear implant patients.

Background: Hearing loss is associated with a range of poor psychosocial outcomes. Cochlear implants (CI) are an available treatment option for significant hearing loss and have been linked to improved quality of life in patients. Evidence suggests that audiologists lack the skills to appropriately detect, address, and refer for psychosocial needs among patients with hearing loss. The objective of this study is to examine the attitudes and practice patterns related to psychosocial care among audiologists who work with CI users. Methods: A cross-sectional survey was administered to clinical audiologists who work with CI recipients in the United States. The survey evaluated participants' attitudes toward psychosocial services and factors that contribute to their abilities to address the psychosocial needs of their patients. Additionally, participants were surveyed about their practice patterns including the use of psychosocial screeners, clinical protocols regarding psychosocial care, and referral patterns for coordinated psychosocial services. Descriptive statistics were used to summarize survey responses. Results: Sixty-eight audiologists completed the survey. Of these audiologists, a majority (73.6%) held the attitude that most or all CI patients would benefit from psychosocial intervention. Despite clinicians' recognition of psychosocial needs in this population, over 90% of participants reported never screening for psychosocial symptoms. Additionally, a majority of respondents indicated that they seldom refer their patients for psychosocial services, with referrals occurring less than half the time (58%) or never (27%). Additionally, few audiologists reported utilizing protocols or resources for guiding psychosocial practices. Audiologists indicated that the primary factors that influence their psychosocial practices include time available to spend with the patient and their comfort level in counseling. Conclusion: Audiologists working with CI patients recognize the potential benefit of psychosocial intervention in this population. Nevertheless, audiologists encounter barriers in clinical practice which limit their ability to identify and address the psychosocial needs of their patients. Strategies designed to enhance audiologists' capacity to recognize the psychosocial needs of CI users, in addition to improved interprofessional practice on CI teams, implies significant opportunities to improve the provision of patient-centered hearing care.