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Checkpoint blockade can reverse CD8+ T-cell functional exhaustion, and TCF-1 is essential for this process. However, identifying mechanisms that can prevent functional senescence and potentiate CD8+ T-cell persistence in checkpoint blockade non-responsive tumors remains a challenge. We demonstrate that targeting Cbx3/HP1γ causes augmented transcription initiation, chromatin remodeling at Lef1 and Il21r leading to increased transcriptional activity at these loci. Mechanistic studies show LEF-1 and IL-21R are required for Cbx3/HP1γ-deficient CD8+ effector T cells to persist resulting in improved control of ovarian cancer, melanoma and neuroblastoma in pre-clinical models. Cbx3/HP1γ-deficient CD8+ T cells enhanced persistence in the TME facilitates remodeling of the chemokine/receptor landscape that ensures their optimal tumor invasion at the expense of CD4+ Tregs. Thus, CD8+ T cells heightened effector function consequent to Cbx3/HP1γ deficiency may be distinct from functional reactivation by checkpoint blockade, implicating Cbx3/HP1γ as a viable cancer T-cell-based therapy target for resistant, non-responsive solid tumors.

To review and update the subsequent reproductive outcomes in patients with complete, partial, and recurrent hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) at the New England Trophoblastic Disease Center.Patients with complete and partial hydatidiform mole, recurrent hydatidiform mole, and GTN were identified from the Donald P. Goldstein, M.D., Trophoblastic Tumor Registry. Questionnaires regarding subsequent pregnancies were mailed to patients with current mailing addresses available. Additional patient data was obtained from electronic medical records.A total of 2,432 subsequent pregnancies have been reported since 1965. Of those, 1,388 pregnancies were after complete mole, 357 after partial mole, and 667 after GTN. The subsequent reproductive outcomes in patients with complete and partial molar pregnancies and persistent GTN remain similar to those in the general population. However, approximately 1.7% of patients with a prior molar pregnancy had a molar pregnancy in a later gestation. Furthermore, after successful chemotherapy for GTN the incidence of stillbirth was slightly increased to 1.3% in later pregnancies.Patients with molar pregnancies and GTN should expect similar reproductive outcomes as compared to the general population. However, patients receiving chemotherapy for GTN have a slightly increased risk stillbirth in subsequent pregnancies.

IT HAS been estimated that the retail value of goat's milk produced in this country exceeds $100,000,000 annually. A large portion of fluid goat's milk is used for infants, for invalids and for consumption in the home of the producer. Various claims have been made for the superiority of goat's milk over cow's milk. Besley1 states that of the two, goat's milk has larger amounts of albumin and nonprotein nitrogen, greater quantities of vitamin B1, a softer curd and smaller fat globules. Richards2 reports "the fact that goat's milk is alkaline in its reaction while cow's milk is acid, . . .