Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type.

Granulysin is a cytolytic protein expressed in cytotoxic T and natural killer (NK) cells. Abnormal serum levels of granulysin in lymphomas with NK and cytotoxic phenotype have been shown to correlate with tumour progression. In this study, we investigated the expression pattern of granulysin in routine sections of normal and reactive lymphoid tissues as well as in a large series of lymphomas. In normal tissues, granulysin labelled a small population of cells that double immunostaining revealed to belong to the pool of cytotoxic T/NK cells. Among lymphoid neoplasms, the highest expression of granulysin (71%) was found in extranodal NK/T cell lymphomas of nasal type (ENKTL). To note is that 29% of ENKTLs, which were negative for one or more of classical cytotoxic markers strongly expressed granulysin. Furthermore, expression of granulysin was observed in rare cases of T cell lymphomas with a cytotoxic phenotype (i.e. ALK-negative anaplastic large cell lymphoma (26%), enteropathy-associated T cell lymphoma (12%) and peripheral T cell lymphoma, NOS (4%)). None of the investigated non-Hodgkin B cell lymphomas, Hodgkin lymphoma and plasma cell myeloma were granulysin positive. The results suggest granulysin as a novel marker for a subset of cytotoxic NK cell derived malignancies and its usefulness is highlighted in those ENKTLs that lack expression of other cytotoxic markers but retain granulysin expression.

Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes.

The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Because efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in more than 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases, respectively, and PD-L1 but not PD-L2 expression correlated with Epstein-Barr virus in tumor cells. PD-L1 staining was detected in 80% of anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, and follicular dendritic cell sarcoma; 75% of nodular lymphocyte-predominant Hodgkin lymphoma; 53% of primary mediastinal large B-cell lymphoma; 39% of extranodal NK/T cell lymphoma; 26% of peripheral T-cell lymphoma; 10% of diffuse large B-cell lymphoma; and very rare examples of mantle, marginal zone, and small lymphocytic lymphomas. PD-L2 staining was present in 78% of primary mediastinal large B-cell lymphoma but in fewer cases in all other categories including 40% of follicular dendritic cell sarcoma and 7% of anaplastic large cell lymphoma. Our results confirm and extend prior studies of PD-L1 and provide new data of PD-L2 expression in lymphomas. The differential expression patterns in some tumor types and the expression of PD-L2 in the absence of PD-L1 raise the possibility of targeted therapy for additional subsets of patients with lymphoma.

Parasite-induced alteration of diurnal rhythms in a freshwater snail.

The trematode Microphallus sp. alters the behavior of its snail intermediate host, Potamopyrgus antipodarum, in ways that seem to increase transmission to its final host, e.g., waterfowl, and decrease the probability of being eaten by other predators, e.g., fish. The parasite seems to cause the snail to move from the top to the bottom of rocks at about 0900 hr. Waterfowl feed predominantly before 0900 hr, and fish feed predominantly after 0900 hr. In the present study, we tested the hypothesis that Microphallus sp.-infected snails exhibit a change in behavior at around 0900 hr by examining their response to light and vertical orientation before and after 0900 hr. Results demonstrated that uninfected snails generally move toward light, oriented downward, and move a greater distance in the light compared with the dark at all times of day. Microphallus sp.-infected snails behaved differently from uninfected snails in the early morning but similarly to uninfected snails in the late morning with regard to downward orientation and distance moved in response to light. Snails infected with parasites other than Microphallus sp. behaved similarly to uninfected snails during both time periods. These results suggest that Microphallus sp. manipulates the behavior of Potamopyrgus sp. by altering rates of movement in response to light and vertical orientation in a manner consistent with the hypothesized 0900-hr shift.