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Marasmius is a widely represented genus in tropical areas, particularly in the Neotropics, which holds exceptional diversity. Previous studies have shown that traditional sections of the genus (e.g. sensu Singer) are still in conflict with phylogenetic data. This paper addresses some issues concerning morphology at the sectional level, section Neosessiles in particular, with regards to taxonomic concepts and partial phylogenetic relationships of new Neotropical species with interesting combinations of inter-sectional characteristics. Taxa descriptions in this study include Marasmius conchiformis sp. nov., M. conchiformis var. dispar var. nov., M. conchiformis var. lenipileatus var. nov., M. griseoroseus, M. griseoroseus var. diminutus var. nov., M. linderoides sp. nov., and M. longisetosus sp. nov. Some of these taxa have pleurotoid habit, and because this condition is poorly known in Marasmius, we considered it appropriate to look at their phylogenetic placement with respect to other species of the genus. We conducted Bayesian and Maximum Likelihood analyses on ribosomal 28S long subunit (LSU) and internal transcribed spacer (ITS) alignments to verify the singularity of the new taxa and to make an assessment of their relationships, regarding morphology, to other species of Marasmius. Overall, molecular and morphological data do support three new distinctive species and three varieties. Part of our findings also supports the view of some macromorphological and micromorphological characters as being highly homoplasic. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.7 years). After second progression/recurrence (n = 55), continuing ICI-based salvage prolonged survival to 11.6 months (n = 38; P < 0.001), particularly for those with extreme mutation burden (P = 0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and the immune microenvironment. Response to reirradiation was explained by an absence of deleterious postradiation indel signatures (ID8). CTLA4 expression increased over time, and subsequent CTLA4 inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to the reinvigoration of peripheral immune and radiologic responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide a mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology., Significance: Hypermutant RRD-HGG are susceptible to checkpoint inhibitors beyond initial progression, leading to improved survival when reirradiation and synergistic immune/targeted agents are added. This is driven by their unique biological and immune properties, which evolve over time. Future research should focus on combinatorial regimens that increase patient survival while limiting immune toxicity. This article is featured in Selected Articles from This Issue, p. 201., (©2023 American Association for Cancer Research.)

Purpose: Checkpoint inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively for refractory nonhematologic cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch repair deficiency (MMRD)., Patients and Methods: Twenty patients were screened, and 10 were ultimately included in the response cohort of whom nine had TMB >10 mut/Mb (three initially eligible based on MMRD) and one patient had TMB between 5 and 10 mut/Mb., Results: Delayed immune responses contributed to best overall response of 50%, improving on initial objective responses (20%) and leading to 2-year overall survival (OS) of 50% [95% confidence interval (CI), 27-93]. Four children, including three with refractory malignant gliomas are in complete remission at a median follow-up of 37 months (range, 32.4-60), culminating in 2-year OS of 43% (95% CI, 18.2-100). Biomarker analyses confirmed benefit in children with germline MMRD, microsatellite instability, higher activated and lower regulatory circulating T cells. Stochastic mutation accumulation driven by underlying germline MMRD impacted the tumor microenvironment, contributing to delayed responses. No benefit was observed in the single patient with an MMR-proficient tumor and TMB 7.4 mut/Mb., Conclusions: Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated cancers including malignant gliomas. Novel biomarkers identified here need to be translated rapidly to clinical care to identify children who can benefit from checkpoint inhibitors, including upfront management of cancer. See related commentary by Mardis, p. 4701., (©2023 The Authors; Published by the American Association for Cancer Research.)