HLA Class II Histocompatibility Antigen γ Chain (CD74) Expression Is Associated with Immune Cell Infiltration and Favorable Outcome in Breast Cancer

The triple-negative breast cancer (TNBC) subtype, defined as negative for ER, PgR, and HER2, is biologically more aggressive and with a poorer prognosis than the other subtypes, in part due to the lack of suitable targeted therapies. Consequently, identification of any potential novel therapeutic option, predictive and/or prognostic biomarker, or any other relevant information that may impact the clinical management of this group of patients is valuable. The HLA class II histocompatibility antigen γ chain, or cluster of differentiation 74 (CD74), has been associated with TNBCs, and poorer survival. However, discordant results have been reported for immunohistochemical studies of CD74 expression in breast cancer. Here we report validation studies for use of a novel CD74 antibody, UMAb231. We used this antibody to stain a TMA including 640 human breast cancer samples, and found no association with the TNBC subtype, but did find a positive correlation with outcome. We also found associations between CD74 expression and immune cell infiltration, and expression of programmed death ligand 1 (PD-L1). Given that CD74 may play a role in innate immune system responses and the potential of immunotherapy as a viable treatment strategy for TNBCs, CD74 expression may have predictive value for immune checkpoint therapies.

HLA-B27-associated uveitis: an independent disease or a variant of spondyloarthritis?

The paper highlights the relationship between HLA-B27-associated uveitis and spondyloarthritis (SpA). It presents the genetic aspects of inflammation of the eyes and musculoskeletal system, the role of the HLA-B27 histocompatibility antigen, and the contribution of other genes to the development of uveitis and spondylitis. The authors characterize the general pathogenetic mechanisms of the development of these diseases: the importance of factors of innate immunity, proinflammatory cytokines in the initiation of inflammation of the eyes and joints. The detection rate of SpA is analyzed in various forms of uveitis; the predictors of SpA development are identified in the patients. An algorithm is presented, which makes it possible to timely diagnose SpA in the presence of acute anterior uveitis. HLA-B27, inflammation in the ocular anterior chamber, unilateral alternating eye lesions, an acute recurrent course, and uveitis onset at the age of less than 30 years are singled out as the most significant signs associated with SpA in patients with uveitis. The features of the course and the frequency of complications in uveitis with and without SpA are compared. It is shown that exacerbations of uveitis and associated complications occur statistically significantly more frequently in SpA. There is evidence for the need for a close interaction between ophthalmologists and rheumatologists in the management of patients with uveitis.

Identification of a lymphocyte minor histocompatibility antigen in Mauritian cynomolgus macaques

Allogeneic hematopoietic stem cell transplantation can lead to dramatic reductions in human immunodeficiency virus (HIV) reservoirs. This effect is mediated in part by donor T cells that recognize lymphocyte-expressed minor histocompatibility antigens (mHAgs). The potential to mark malignant and latently infected cells for destruction makes mHAgs attractive targets for cellular immunotherapies. However, testing such HIV reservoir reduction strategies will likely require preclinical studies in nonhuman primates (NHPs). In this study, we used a combination of alloimmunization, whole exome sequencing, and bioinformatics to identify a mHAg in Mauritian cynomolgus macaques (MCMs). We mapped the minimal optimal epitope to a 10-mer peptide (SW10) in apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3) and determined the major histocompatibility complex class I restriction element as Mafa-A1*063, which is expressed in almost 90% of MCMs. APOBEC3C SW10-specific CD8+ T cells recognized immortalized B cells but not fibroblasts from a mHAg positive MCM. These results collectively provide a framework for identifying mHAgs in a nontransplant setting and suggest that APOBEC3C SW10 could be used as a lymphocyte-restricted model antigen in NHPs to test various mHAg-targeted immunotherapies.ImportanceCellular immunotherapies developed to treat blood cancers may also be effective against latent HIV. Preclinical studies of such immunotherapies are hindered by a lack of known target antigens. We used a combination of alloimmunization, basic immune assays, whole exome sequencing, and bioinformatics to identify a lymphocyte-restricted minor histocompatibility antigen in a genetically related population of nonhuman primates. This minor histocompatibility antigen provides an actionable target for piloting cellular immunotherapies designed to reduce or eliminate latent reservoirs of HIV.