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Hui Yu Zhengming Chen Karla V. Ballman Mark A. Watson Ramaswamy Govindan Irena Lanc David G. Beer Raphael Bueno Lucian R. Chirieac Michael Herman Chui Guoan Chen Wilbur A. Franklin David R. Gandara Carlo Genova Kristine A. Brovsky Mary-Beth M. Joshi Daniel T. Merrick William G. Richards Fred R. Hirsch 《Journal of thoracic oncology》2019,14(1):25-36
Objectives
Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.Methods
A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.Results
The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.Conclusions
Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells. 相似文献105.
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C H Hirsch L Sommers A Olsen L Mullen C H Winograd 《Journal of the American Geriatrics Society》1990,38(12):1296-1303
This study provides data on changes in the functional status of older patients that are associated with acute hospitalization. Seventy-one patients over the age of 74 admitted to the medical service of Stanford University Hospital between February and May 1987 received functional assessments covering seven domains: mobility, transfer, toileting, incontinence, feeding, grooming, and mental status. Assessments were obtained by report from the patient's caregiver (or the patient when he or she lived alone) for 2 weeks before admission; from the patient's nurse on day 2 of hospitalization and on the day before discharge; and again from the caregiver (or patient) 1 week after discharge. The sample had a mean age of 84, covered 37 Diagnostic Related Groups, and had a median length of stay of 8 days. Between baseline and day 2, statistically significant deteriorations occurred for the overall functional score and for the individual scores for mobility, transfer, toileting, feeding, and grooming. None of these scores improved significantly by discharge. In the case of mobility, 65% of the patients experienced a decline in score between baseline and day 2. Between day 2 and discharge, 67% showed no improvement, and another 10% deteriorated further. These data suggest that older patients may experience a burden of new and worsened functional impairment during hospitalization that improves at a much slower rate than the acute illness. An awareness of delayed functional recovery should influence discharge planning for older patients. Greater efforts to prevent functional decline in the hospitalized older patient may be warranted. 相似文献
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A Sauerbrei P Wutzler I F?rber K Wutke B Brichacek I Hirsch 《Archiv fuer geschwulstforschung》1987,57(6):445-452
Tumor tissue specimens of 25 patients with various entities of Non-Hodgkin's lymphomas were examined for the presence of Epstein-Barr virus (EBV) nucleic acids and EBV nuclear antigens (EBNA) by in situ hybridization and anticomplement immunofluorescence. In tumor cells of five patients EBV nucleic acid and EBNA were demonstrated. The histopathologic examinations revealed in these cases one Burkitt's lymphoma, two centroblastic lymphomas and each one lymphoplasmocytic and lymphocytic lymphoma. 相似文献
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Prediction of major cardiac events after peripheral vascular surgery using dipyridamole echocardiography 总被引:1,自引:0,他引:1
M D Tischler T H Lee A T Hirsch C P Lord L Goldman M A Creager R T Lee 《The American journal of cardiology》1991,68(6):593-597
Patients undergoing peripheral vascular surgery are at increased risk of postoperative cardiac complications. To evaluate the role of dipyridamole echocardiography in predicting major cardiac events, 109 unselected patients undergoing elective peripheral vascular surgery were prospectively studied. Preoperative dipyridamole echocardiograms were interpreted by an echocardiographer unaware of all clinical data. Patients were followed up until hospital discharge by research physicians without knowledge of dipyridamole echocardiography results. Outcomes were classified using strict predefined criteria by reviewers unaware of other clinical and echocardiographic data. Of the 109 patients, 9 (8%) had positive studies defined as development of new regional wall motion abnormalities or worsening of preexistent wall motion abnormalities. Of these 9 patients, 7 had postoperative events, including 3 cardiac deaths, 1 nonfatal myocardial infarction, 2 with unstable angina, and 1 with pulmonary edema. Only 1 event occurred among the 100 patients with negative studies. The sensitivity and specificity of dipyridamole echocardiography for predicting cardiac events after vascular surgery were 88 and 98%, respectively; the positive and negative predictive values were 78 and 99%. The relative risk of having a cardiac event if dipyridamole echocardiography was abnormal was 78 (95% confidence interval, 11 to 564; p less than 0.0001). If these results are extended and confirmed by other investigators, preoperative dipyridamole echocardiography may be an important screening test for patients undergoing elective peripheral vascular surgery. 相似文献