Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microenvironment that is rich in nonmalignant immune cells. We applied single-cell RNA sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T cells, including a cytotoxic CD4 T-cell population. We characterized four major FL subtypes with differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associated with significant differences in the proportions and targetable immunophenotypic characteristics of T cells. This provides a classification framework of the FL microenvironment in association with FL genotypes and MHC expression, and informs different potential immunotherapeutic strategies based upon tumor cell MHCII expression. Significance: We have characterized the FL-infiltrating T cells, identified cytotoxic CD4 T cells as an important component that is associated with tumor cell–intrinsic characteristics, and identified sets of targetable immune checkpoints on T cells that differed from FLs with normal versus low MHC expression. See related commentary by Melnick, p. 374. This article is highlighted in the In This Issue feature, p. 369

Despite major scientific discoveries and novel therapies over the past four decades, the treatment outcomes of acute myeloid leukemia (AML), especially in the adult patient population remain dismal. In the past few years, an increasing number of targets such as CD33, CD123, CLL-1, CD47, CD70, and TIM3, have been developed for immunotherapy of AML. Among them, CLL-1 has attracted the researchers’ attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 is an ideal target for AML. In this paper, we will review the expression of CLL-1 on normal cells and AML, the value of CLL-1 in diagnosis and follow-up, and targeting CLL-1 therapy-based antibody and chimeric antigen receptor T cell therapy as well as providing an overview of CLL-1 as a target for AML.

We retrospectively analyzed the outcomes of all consecutive patients with myeloma (n = 84) aged ≥70 years who had received autologous hematopoietic stem cell transplant (auto HCT) between July 1999 and June 2010 at our institution. The median age at auto HCT was 72 years, the median number of prior therapies was 2.5 and the median time from diagnosis to auto HCT was 10.2 months. The conditioning regimen consisted of melphalan at 140 mg/m² in 10%, 180 mg/m² in 25% and 200 mg/m² in 65% of patients. The day-100 non-relapse mortality was 3%. The overall response rate at day 100 was 85% (complete response 18%, very good partial response 12%, partial response 55%). After a median follow-up of 25 months among surviving patients, the estimated progression-free survival and overall survival at 5 years were 27% and 67%, respectively. The incidence of grade II–IV toxicity, response rate and survival were similar across three melphalan dose levels. These results indicate that high-dose melphalan plus auto HCT is safe and feasible for patients with multiple myeloma aged ≥70 years and age alone should not be an exclusion criterion for auto HCT.

Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution

Dasatinib, a dual Src/Abl tyrosine kinase inhibitor, has significant antileukemic effects against various imatinib mesylate-resistant BCR/ABL mutants. Despite well-documented inhibitory effects of dasatinib on BCR/ABL kinase, the exact downstream cellular events leading to generation of its potent antileukemic effects remain to be defined. We provide evidence that p38 Map kinase (MAPK) pathway is activated leading to increased upregulation of mixed lineage kinase 3, MKK3/6, MSK1, and Mapkapk2, upon treatment of BCR/ABL expressing cells with dasatinib, including cells expressing various imatinib-resistant mutants, except for T315I. Our data demonstrate that such dasatinib-dependent activation of p38 MAPK and its effectors plays a critical role in the generation of antileukemic responses, since pharmacological inhibition of p38 or siRNA-mediated knockdown of its expression reverse dasatinib-mediated apoptosis, cell cycle arrest, and anti-proliferative effects. p38 MAPK inhibition also reversed dasatinib-induced suppression of CML patient-derived leukemic colony-forming units progenitor growth in vitro, as well as BCR/ABL expressing KT-1 cell-derived leukemic progenitor growth. Altogether, our findings suggest a critical role for p38 MAPK pathway in the generation of antileukemic effects of dasatinib, and raise the possibility that development of novel means to enhance p38 MAPK activation in BCR/ABL expressing cells may be an approach to promote antileukemic responses and, possibly, reverse T315I mutation-mediated resistance.