RESUMO
PURPOSE: Immune checkpoint inhibition (ICI) therapy represents one of the great advances in the field of oncology, highlighted by the Nobel Prize in 2018. Multiple predictive biomarkers for ICI benefit have been proposed. These include assessment of programmed death ligand-1 expression by immunohistochemistry, and determination of mutational genotype (microsatellite instability or mismatch repair deficiency or tumor mutational burden) as a reflection of neoantigen expression. However, deployment of these assays has been challenging for oncologists and pathologists alike. METHODS: To address these issues, ASCO and the College of American Pathologists convened a virtual Predictive Factor Summit from September 14 to 15, 2021. Representatives from the academic community, US Food and Drug Administration, Centers for Medicare and Medicaid Services, National Institutes of Health, health insurance organizations, pharmaceutical companies, in vitro diagnostics manufacturers, and patient advocate organizations presented state-of-the-art predictive factors for ICI, associated problems, and possible solutions. RESULTS: The Summit provided an overview of the challenges and opportunities for improvement in assay execution, interpretation, and clinical applications of programmed death ligand-1, microsatellite instability-high or mismatch repair deficient, and tumor mutational burden-high for ICI therapies, as well as issues related to regulation, reimbursement, and next-generation ICI biomarker development. CONCLUSION: The Summit concluded with a plan to generate a joint ASCO/College of American Pathologists strategy for consideration of future research in each of these areas to improve tumor biomarker tests for ICI therapy.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Idoso , Estados Unidos , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Instabilidade de Microssatélites , Patologistas , Medicare , Biomarcadores Tumorais/genética , Neoplasias/diagnósticoRESUMO
BACKGROUND: CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy. METHODS: Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)). RESULTS: ITGAE was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ TRM cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion. CONCLUSIONS: Our analyses indeed demonstrate that the presence of CD103+ CD8+ TRM cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD/genética , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Cadeias alfa de Integrinas/genética , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos do Interstício Tumoral/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/imunologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Fenótipo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Microambiente Tumoral , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologiaRESUMO
PURPOSE: Lower pole renal access during flexible ureterorenoscopy is often limited by the active deflection capabilities of the ureteroscope. Deterioration in the deflection and flow capabilities of ureteroscopes occurs with the passage of instrumentation through the working channel. We performed in vitro evaluation of a novel technique using unsheathed nitinol baskets to minimize the deterioration in deflection and maximize the irrigant flow associated with instrument passage through the working channel during flexible ureterorenoscopy. MATERIALS AND METHODS: Alterations in the irrigant flow and active deflection of 4 ureteroscopes from different manufacturers were evaluated. Each ureteroscope was evaluated with an empty working channel, and then with sheathed and unsheathed 2.2, 3 and 3.2Fr (Cook Urological, Inc., Indianapolis, Indiana), 2.4 and 3Fr (Microvasive Urology, Natick, Massachusetts) nitinol baskets in the working channel. RESULTS: With all baskets tested and in all ureteroscopes the deterioration in active deflection and irrigant flow was improved with the unsheathed baskets. The disassembled basket within the working channel allowed an additional 15 to 20 degrees of active deflection. In addition, the disassembled basket allowed for a 2 to 30-fold increase in irrigant flow compared with an intact basket. CONCLUSIONS: The combination of improved deflection and irrigant flow with this technique may improve ureteroscopic access to lower pole renal calculi.