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Monoclonal antibodies that target specific ligand-receptor signaling pathways and act as immune checkpoint inhibitors have been designed to remove the brakes in T cells and restore strong and long-term antitumor-immunity. Of note, many of these inhibitory receptors are also expressed by Innate Lymphoid Cells (ILCs), suggesting that also blockade of inhibitory pathways in innate lymphocytes has a role in the response to the treatment with checkpoint inhibitors. ILCs comprise cytotoxic NK cells and "helper" subsets and are important cellular components in the tumor microenvironment. In addition to killing tumor cells, ILCs release inflammatory cytokines, thus contributing to shape adaptive cell activation in the context of immunotherapy. Therefore, ILCs play both a direct and indirect role in the response to checkpoint blockade. Understanding the impact of ILC-mediated response on the treatment outcome would contribute to enhance immunotherapy efficacy, as still numerous patients resist or relapse.

Different studies have evaluated the comparability of various immunohistochemical assays for PD-L1 expression evaluation, with contrasting results. Besides the important issues related to analytic performance and comparability of validated assays, not all platforms are available in all laboratories; moreover, standardized assays are very expensive, and funding for PD-L1 testing is hard to obtain, especially in the research setting. One of the most widely used and inexpensive PD-L1 clones is E1L3N (Cell Signaling Technology, Danvers, MA), which is labeled for research use only. In this work, we wanted to further study and validate in a larger cohort the analytical performance of E1L3N clone on Ventana platform (Ventana Medical Systems, Tucson, AZ) and its comparability with assays SP263 and 22C3 run onto their dedicated platforms. Serial sections of tissue microarrays built from 165 cases of resected lung cancer were stained for E1L3N onto Ventana platform following a previously reported protocol and for 22C3 and SP263 assays onto their respective platforms following manufacturer's instructions. Overall, we found very high concordance when comparing E1L3N with SP263 at both 1% and 50% cutoffs. Lower concordance was found between E1L3N and 22C3 at both cutoffs; however, 100% sensitivity was found for E1L3N compared with both SP263 and 22C3 at 50% cutoff. Given the 100% sensitivity at 50% cutoff demonstrated by E1L3N in comparison with both SP263 and 22C3 and therefore the lack of false-negative cases, we propose an algorithm for PD-L1 testing in NSCLC when considering pembrolizumab as first-line therapy.

Pancreatic ductal adenocarcinoma (PDAC) and its variants comprise between 80% and 90% of all tumors of the exocrine pancreas. Because of its silent course, late clinical manifestation, and rapid growth, it is considered a silent killer. Only 10% to 15% of cases are resectable and the 5-year survival rate remains lower than 5%. The differential diagnosis between PDAC and chronic pancreatitis is a challenge for pathologists. This article provides a guide for pathologic evaluation of PDAC specimens with the macroscopic and microscopic features of common PDAC and its variants and discusses the differential diagnosis and morphologic and immunophenotypical prognostic parameters.

Prediction for malignancy of pancreatic endocrine tumors (PET) is often a formidable challenge for the pathologist. The authors evaluated the role of the proliferative activity and progesterone receptor protein (PgRP) in predicting prognosis and survival of PET. Twenty-three functioning (FT) and 31 nonfunctioning tumors (NFT) were evaluated for mitotic activity and immunostaining for Ki-67 antigen, proliferating cell nuclear antigen (PCNA), and progesterone receptor protein (PgRP) on paraffin sections. The results were expressed as a percentage (index) of immunoreactive or mitosing cells. All 54 cases showed immunostaining for Ki-67 and PCNA, and valuable mitotic index, whereas only a fraction of tumors (25 of 54 cases) exhibited PgRP expression. Ki-67 and PCNA indexes correlated strongly between themselves and to mitotic index, whereas an inverse relationship was observed between cell proliferation and PgRP status in both FT and NFT. Although univariate analysis showed that Ki-67, PCNA, mitotic and PgRP indexes, stage, immunoreactivity for hormones other than insulin, diameter, and nonfunctioning type of tumor were statistically correlated to survival, Cox's regression method let only Ki-67 index emerge as an independent predictor of survival using a cutoff value of 5% in both FT and NFT.