RESUMEN
BACKGROUND AND OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor response to systemic therapies, including immunotherapy. Given the immunotherapeutic potential of natural killer (NK) cells, we evaluated intratumoral NK cell infiltrates along with cytotoxic T cells in PDAC to determine their association with patient outcomes. METHODS: We analyzed tumors from 93 PDAC patients treated from 2012 to 2020. Predictor variables included tumor-infiltrating lymphocytes (TILs), T-cell markers (CD3, CD8, CD45RO), NK marker (NKp46), and NK inhibitory marker (major histocompatibility complex class I [MHC-I]) by immunohistochemistry. Primary outcome variables were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Mean TILs, CD3, and NKp46 scores were 1.3 ± 0.63, 20.6 ± 17.5, and 3.1 ± 3.9, respectively. Higher expression of CD3 and CD8 was associated with higher OS, whereas NK cell infiltration was not associated with either RFS or OS. There was a tight positive correlation between MHC-I expression and all T-cell markers, but not with NKp46. CONCLUSIONS: Overall NK cell infiltrates were low in PDAC and did not predict clinical outcomes, whereas T-cell infiltrates did. Further characterization of the immune infiltrate in PDAC, including inhibitory signals and suppressive cell types, may yield better biomarkers of prognosis and immune targeting in this refractory disease.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Linfocitos T Citotóxicos/metabolismo , Linfocitos T Citotóxicos/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor , Células Asesinas Naturales , Pronóstico , Linfocitos T CD8-positivosRESUMEN
BACKGROUND: As the US demographic evolves, surgical fields must adapt to ensure equitable healthcare. Healthcare disparities notably affect minority populations, with communities of color often facing physician shortages and higher rates of diseases such as coronary disease, stroke, and cancer. Research shows that minority physicians significantly improve patient satisfaction and outcomes in underserved communities, highlighting the need for increased physician diversity to enhance cultural competency and patient centered care. Data from the Association of American Medical Colleges (AAMC) reveals minimal increases in underrepresented minorities (URM) in surgical residency and academic careers over the past thirty-six years, with little change URM applicants and matriculants in the nine surgical specialties recognized by the American College of Surgeons from 2010 to 2018. OBJECTIVE: This review aims to critically evaluate the current landscape of racial and gender diversity in six out of the nine defined surgical specialties (general surgery, plastic surgery, neurosurgery, orthopedic surgery, cardiothoracic surgery, and vascular surgery) in the US. DESIGN: We conducted a comprehensive literature review to assess of the state of diversity within surgical specialties in the United States. By analyzing the benefits of diversity in surgical fields, evaluating the effectiveness of various diversity programs and initiatives, examining the comparative diversity between surgical subspecialties, and assessing the impact of diversity on patient outcomes, our aim is to highlight the critical importance of enhancing diversity in surgical fields. RESULTS: While nuances in representation and diversity vary across surgical specialties, all fields persistently exhibit underrepresentation of certain racial/ethnic groups and persistent gender disparities. These disparities manifest throughout various phases, including in residency, and in the recruitment and retention of URM individuals in surgery and surgical subspecialties. While interventions over the past decade have contributed to improving diversity in surgical fields, significant disparities persist. Limitations include the time required for recent interventions to show significant impacts and the inability of established interventions to eliminate disparities. CONCLUSIONS: Despite the clear benefits, diversity within surgical specialties remains an uphill battle. Addressing the diversity gap in surgical fields is crucial for improving patient outcomes, healthcare access, and workplace environments, requiring strategies such as targeted recruitment, mentorship programs, and addressing systemic biases. This review highlights the undeniable imperative for change and serve a call to action.
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Diversidad Cultural , Grupos Minoritarios , Especialidades Quirúrgicas , Especialidades Quirúrgicas/educación , Humanos , Estados Unidos , Grupos Minoritarios/estadística & datos numéricos , Predicción , Masculino , FemeninoRESUMEN
Introduction: Soft tissue sarcomas (STS) are rare, heterogenous malignancies with an unmet need for novel immunotherapies. Tumor infiltrating lymphocytes (TILs) have been linked with favorable outcomes in STS patients, though the contribution of natural killer (NK) cells and spatial relationships of TILs with MHC-I expressing cells lacks detailed characterization. Experimental design: Using archived and prospectively collected specimens, we evaluated intratumoral NK cells by immunohistochemistry (IHC), flow cytometry, and immunofluorescence (IF). We assessed spatial localization of NK and T cells by multiplex IF, analyzing the effects of MHC-I expression status on NK and T cell clustering. Results: Both intratumoral NKp46 and CD56dim expression were associated with significantly improved overall survival (P=0.05), while higher infiltrates of CD56bright NK cells predicted a worse prognosis (P=0.05). The presence of intratumoral NK cells was inversely proportional to CD3+ T cells. Spatial analyses showed NK cells preferentially clustering close to other NK cells with sparse CD3+ T and CD8+ T cells in range (P<0.0001). Additionally, CD3+ T and CD8+ T cells showed significantly greater co-localization with MHC-I+ cells, compared to NK cells (P<0.0001). After neoadjuvant radiotherapy, there was greater CD8 clustering, while after neoadjuvant chemotherapy, there was overall lower TIL clustering. Conclusion: Intratumoral NK cells are prognostic in STS and localize closer to MHC-I- cells than T cells. Although both NK and T cells are associated with improved survival in STS, their differential distribution in the TME based on MHC-I expression status may serve as a biomarker for improved immunotherapy treatment selection.
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Linfocitos T CD8-positivos , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Linfocitos T CD8-positivos/inmunología , Células Asesinas Naturales/inmunología , Pronóstico , Sarcoma/inmunología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/inmunología , Neoplasias de los Tejidos Blandos/terapiaRESUMEN
At the outset of the coronavirus pandemic, before we had a chance to acclimate to our world turned upside-down, I was genuinely confounded by the inflexibility of some professors to help students. After all, we had been offered the grace of an extension on tenure-track requirements, and afforded the opportunity, and relative safety, of working from home. How was it possible then, to not understand that students, too, might need grace? And how could anyone be OK with choosing not to help? Far from traditional research questions, my wonderings provoked lively conversations with colleagues, and a lens through which to consider my own positionality and difficulties in dealing with the challenges posed by the pandemic. Framed by Nel Noddings' Ethic of Care, and through poetic inquiry, this article presents a personal response to teaching in an Educator Preparation Program during a global pandemic.