The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown. One hundred two cases of NSCLC (51 adenocarcinomas, 9 adenosquamous carcinomas, and 42 squamous cell carcinomas) were evaluated for IDO-1 and PD-L1 expression by immunohistochemistry. IDO-1 expression was identified in 43% of NSCLC (42% of adenocarcinomas, 44% of adenosquamous carcinomas, and 43% of squamous cell carcinomas). Coexpression with PD-L1 (≥1%) was common (27% overall; 27% of adenocarcinomas, 33% of adenosquamous carcinomas, and 26% of squamous cell carcinomas). A smaller population of tumors showed isolated PD-L1 (25% overall; 16% of adenocarcinomas, 44% of adenosquamous carcinomas, and 33% of squamous cell carcinomas) or IDO-1 expression (15% overall; 14% of adenocarcinomas, 11% of adenosquamous carcinomas, and 17% of squamous cell carcinomas). In summary, IDO-1 is commonly expressed by NSCLC, and its frequent coexpression with PD-L1 may account for the increased efficacy seen with dual blockade of PD-1/PD-L1 and IDO in clinical studies. IDO-1 immunohistochemistry may be a useful biomarker for selection of patients who could benefit from dual-agent therapy and should be evaluated in prospective clinical trials using PD-1/PD-L1 and IDO inhibitors.
It is becoming increasingly important to obtain detailed diagnostic information on small-volume tissue biopsies, such as core needle biopsies. This is particularly crucial in the workup and diagnosis of classic Hodgkin lymphoma (CHL) and other morphologically similar lymphomas such as T-cell/histiocyte-rich large B-cell lymphoma (THRLBL), where small-volume lymph node biopsies often represent the frontline tissue source, and the differential diagnosis includes a reactive process. Immunohistochemical markers could be helpful to differentiate CHL from reactive lymph node changes (RLN) in this setting. The use of programmed cell death-1 (PD-1) and its ligand (PD-L1) immunohistochemistry has historically focused on prognostic and therapeutic value when evaluating CHL. However, the present study seeks to determine the diagnostic utility of these markers in core needle biopsies of CHL (25), THRLBL (3), and RLN (31). The cases of CHL and THRLBL were previously diagnosed and confirmed with standard immunohistochemistry, allowing the utility of PD-1 and PD-L1 to be tested in this setting. Different PD-1 and PD-L1 expression patterns were observed between the reactive process of RLN and the malignant lymphomas (CHL and THRLBL). CHL cases overall showed the greatest expression of PD-L1 within the malignant Reed-Sternberg cell population, with 40% of CHL cases exhibiting >50% PD-L1 expression. This degree of PD-L1 expression was not seen in the lymphocytic cell population of any RLN (P<0.001). Conversely, CHL cases showed an overall lower expression of PD-1, as 96% of CHLs had <5% PD-1 expression in Reed-Sternberg cells compared with only 10% expression within the lymphocytic population of RLN (P<0.001). THRLBL cases followed a similar trend to CHL. These results demonstrate that upfront PD-1 and PD-L1 immunohistochemistry can aid in the diagnosis of CHL in small-volume tissue biopsies.
Background: Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL).
Methods:The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial
FL diagnosis and suspected recurrence or transformation of FL. A total of 676This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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