Bo-Jung Chen

Current research primarily focuses on post-treatment resistance, leaving the immediate impact of cisplatin on the tumor–immune interaction poorly understood. Tumor cells were co-cultured with immune cells to assess immune cell activation. The correlation with RAB27A/B and CD274 expression levels in non-small cell lung cancer (NSCLC) were analyzed using TCGA. The relationship between RAB27A/B and the tumor microenvironment was assessed by TIMER2.0. Cisplatin significantly increased PD-L1 mRNA levels and surface protein expression, detected by qPCR, flow cytometry and confocal microscopy. In the co-culture assay, cisplatin-induced cell surface PD-L1 protein levels inhibited the activation of Jukat T-cells. Cisplatin also upregulated genes associated with exosome secretion and increased total exosome particle counts and secretion per cell. Pretreatment with GW4869, an exosome release inhibitor, significantly enhanced cisplatin sensitivity in HCC827 cells. While GW4869 reduced intracellular RAB27A/B and EV PD-L1 levels, it did not alter cellular PD-L1 expression. Bioinformatic analysis further revealed that high RAB27A/B expression correlates with poor 5-year survival in NSCLC and is negatively associated with CD8+ T-cell activation, while positively correlating with cancer-associated fibroblasts. Both RAB27A and RAB27B gene expression levels positively correlated with CD274. Conclusions: RAB27A and RAB27B may be crucial proteins in modulating cisplatin-induced exosomal PD-L1 levels and the tumor microenvironment.

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Although most T-cell neoplasms that develop in HTLV-1 carriers are considered ATLL, non-ATLL T-cell lymphomas (TCLs) could also occur, as documented in only a few case reports. Herein, we presented 14 cases of non-ATLL TCLs arising in HTLV-1 carriers. All TCL cases were serologically positive for HTLV-1 antibody; Southern blot analysis for the viral integration of HTLV-1, in situ hybridization for HTLV-1 basic leucine zipper factor (HBZ-ISH), quantitative real-time PCR for HTLV-1 proviral load (HTLV-1-qPCR), the entire HTLV-1 genome sequence, and target capture sequencing rigorously excluded the possibility of ATLL. Various histological subtypes, such as six nodal T follicular helper cell lymphomas, angioimmunoblastic type/not otherwise specified (nTFHL-AI/NOS), two monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL), two peripheral T-cell lymphomas, NOS (PTCL, NOS), and two anaplastic large cell lymphomas (ALCL), ALK-negative, were included. Each case exhibited immunophenotypes and genetic profiles consistent with its respective histological subtype, but atypical for ATLL. Three nTFHL-AI cases exhibited co-mutations of RHOA p.G17V, TET2, and IDH2 p.R172, characteristic of nTFHL-AI but not of ATLL. Among the molecular analytic modalities included in this study, the combination of HBZ-ISH and HTLV-1-qPCR represented the results obtained from the other more expensive modalities, indicating that this combination is effective in daily practice. When T-cell neoplasms arise in HTLV-1 carriers and exhibit atypical clinical, phenotypical, or genetic features for ATLL, it is recommended to perform HBZ-ISH and HTLV-1-qPCR to distinguish non-ATLL TCLs.

Primary cutaneous T-cell lymphoma is distinct from nodal T-cell lymphoma clinically and pathologically. Recently, primary cutaneous follicular helper T-cell lymphoma (PC-TFHL) has been described as a peripheral T-cell lymphoma with T-follicular helper (TFH) cell phenotype. PC-TFHL usually presents as multiple plaques and nodules of skin with an indolent clinical course, but without association with Epstein–Barr virus. In this article, we report 2 rare cases of PC-TFHL which are Epstein–Barr virus–positive and with an aggressive clinical course. We discuss the challenges in the differential diagnoses, particularly with primary cutaneous extranodal NK/T-cell lymphoma, and nodal T-cell lymphoma of TFH origin with secondary cutaneous involvement.

High-risk human papillomavirus (HPV) infections and epidermal growth factor receptor (EGFR) expression have been reported to be associated with more favorable survival outcomes in lung adenocarcinoma patients. In this study, we utilized transfected HPV 16E5/16E6/16E7 H292 cells to investigate the mechanism of HPV oncoproteins interfering with EGFR nuclear trafficking related to a better response to cisplatin. Furthermore, we correlated HPV 16E6/18E6 expression and differentially localized EGFR expression with the clinical association and survival impact in lung adenocarcinoma patients. Our results found significantly higher phosphorylated nuclear EGFR expression upon epidermal growth factor stimulus and better responses to cisplatin in transfected HPV 16E5/16E6/16E7 NCI-H292 cells and xenograft animal models. Our data were compatible with clinical results of a high correlation of HPV 16E6/18E6 and EGFR expression in non-small cell lung cancer tissues and the synergistic effects of both with the best survival prognosis in a lung adenocarcinoma cohort, especially in patients with older age, no brain metastasis, smoking history, and wild-type EGFR status. Cumulatively, our study supports HPV 16E5/16E6/16E7 oncoproteins interfering with EGFR nuclear trafficking, resulting in increased sensitivity to cisplatin. HPV 16E6/18E6 and EGFR expression serve as good prognostic factors in lung adenocarcinoma patients.

Primary effusion lymphoma (PEL) is defined by the WHO classification as a large B-cell neoplasm without detectable tumor masses. It is universally associated with HHV8, with most cases occurring in the setting of immunodeficiency such as HIV infection, and a poor prognosis. Morphologically, the neoplastic cells range from immunoblastic, plasmablastic, to anaplastic; and phenotypically, most cases express plasma cell but not B-cell markers, i.e., plasmablastic. During the past decade, primary HHV8-negative effusion lymphoma has been reported. Such cases were considered in the WHO classification scheme as effusion-based lymphoma. We performed a systemic review of 167 HHV8-negative effusion lymphomas from the literature and found that only 42% were associated with a fluid overload state, and with low rates of HIV (6%) or EBV (21%) infection. Furthermore, most patients are old (or immunosenescent) with underlying medical conditions/comorbidities, most neoplasms are of B-cell phenotype, and the outcome is more favorable than that of HHV8-positive PEL. These distinctive findings supported our prior proposal of designating these HHV8-negative cases as type II PEL, in contrast to the classic or type I PEL as defined by the WHO. Furthermore, we propose an algorithmic approach for the diagnosis of PEL and its mimickers.

J Indian Prosthodont Soc, Official publication of Indian Prosthodontic Society