B cell maturation antigen (BCMA)-directed CAR-T cell therapy is a disruptive approach for treating relapsed/refractory multiple myeloma (R/R MM); however, optimization is necessary to maximize patient benefit. We report the case of a 61-year-old woman with primary refractory MM who presented with high expression of membrane BCMA and low expression of soluble BCMA (sBCMA), experienced grade 4 cytokine release syndrome, and died fromsevere pneumonia after receiving anti-BCMA CAR-T (CT103A) therapy. This case highlights the importance of assessing the expression range of BCMA for its efficacy and safety in patients receiving BCMA CAR-T therapy. For patients who present with extremely high membrane BCMA expression and extremely low sBCMA expression, the presence of γ-secretase-related gene mutations should be considered. Special attention should also be paid to the prevention and treatment of cytokine release syndrome in such patients.

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3-CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case-control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3-CD56+ and CD8+CD57+ cells and sub-populations of CD3-CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94-4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82-2.45); p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral blood CD3-CD56+ and CD8+CD57+ cells in the preconception period does not reflect the risk of implantation failure or miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large studies are needed to develop a reliable peripheral blood marker of immune deregulation.

Although much emphasis is given to the use of immune checkpoint inhibitors to restore the functionality of exhausted lymphocytes, very little is known about the fate of cancer cells that escape from the cytotoxic activity of T cells. In a previous issue of Cancer Research, Stein and colleagues investigated the response of cancer cells to CD8+ T cells disarmed of their killing activity. Spared cancer cells acquired stem cell-like features and displayed an enhanced capacity to form tumors and metastasize. These increased tumorigenic properties could represent the other side of the coin of T-cell surveillance seen in wound healing in which recognition of damaged tissue as \"self\" gives the green light for healing process.See related article by Stein and colleagues; Cancer Res 79(7):1507-19.

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease (EBV+ T-LPD) is extremely rare. Primary acute or chronic active Epstein-Barr virus infection triggers EBV+ T-LPD\'s onset and the disease involves clonal proliferation of infected T-cells with activated cytotoxic phenotype. The adult-onset EBV+ T-LPD (ASEBV+ T-LPD) is even rarer and needs to be extensively studied. Further, according to literature review, it is a challenge to find patients who are immunocompetent and diagnosed with ASEBV+ T-LPD involving gastrointestinal tract. This case report discusses a previously healthy middle aged woman who presented with unique symptoms mimicking inflammatory bowel disease, and required a total colectomy and terminal ileum rectomy, as reveled by endoscopic examinations, due to severe gastrointestinal bleeding. Post-surgery histopathological findings were confirmatory for the diagnosis of ASEBV+ T-LPD (II: Borderline). This patient died 7 months after the diagnosis.

The aim of this case- control study was to investigate the association between preterm birth (PTB), MICA-129 A/G dimorphism and sMICA levels. Fifty pregnant women with singleton pregnancy and previous PTB, or clinic diagnostic of threatened preterm labor in the actual pregnancy, or cervical length less than 25 mm and 50 healthy pregnant women were enrolled. DNA was extracted for genotyping for MICA-129 A/G by real-time PCR and sMICA plasma level was quantified by sandwich ELISA assay. Clinical and socioeconomic characteristics, results of TaqMan® genotyping and ELISA quantification were compared between the groups using qui-square, Fisher´s exact or Mann-Whitney test. A binary logistic regression model was used to predict PTB. The correlation between MICA-129 A/G genotypes and sMICA levels was investigated. There were not statistically significant differences between MICA-129 A/G polymorphism and sMICA plasma level.There was found a correlation between MICA-129 val/val genotype and higher levels of sMICA (ρ: -0.342; p:0.001). The presence of MICA-129  val/val genotype may be influencing sMICA expression.

T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.

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The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials.

OBJECTIVE: Does addition of enoxaparin to sildenafil and etanercept immunotherapy improve IVF outcome?
METHODS: Report of a striking case with 15 IVF failures.
RESULTS: When enoxaparin was added, the 16th IVF cycle generated a healthy male baby.
CONCLUSIONS: Combination therapy that includes a heparin may allow successful IVF outcome and this issue merits further study.