Immune Characteristics of Chinese Diffuse Large B-Cell Lymphoma Patients: Implications for Cancer Immunotherapies.

Immunotherapeutic agents have demonstrated encouraging signs of clinical utility in non-Hodgkin lymphoma. The goal of this study is to analyze the immune characteristics of Chinese patients with diffuse large B-cell lymphoma (DLBCL) to inform the development of immunotherapies in this patient population. Tumor samples from 211 DLBCL patients were analyzed for cell of origin (COO) and immune characteristics using the NanoString platform as well as MYC protein expression through immunohistochemistry. Lower incidence of the germinal center B-cell (GCB) subtype (93/211, 44.1%) was observed in this cohort. Compared to the GCB subtype, the activated B-cell (ABC) subtype was associated with significantly increased expression of multiple pro-inflammatory gene signatures and decreased expression of anti-inflammatory gene signatures. Instead of affecting the pro-inflammatory genes, MYC protein overexpression showed a negative correlation with the expression of T-cell receptor (TCR) and T regulatory genes as well as the OX40 gene. Regardless of COO, higher PD-L1 or IDO1 gene expression correlated with increased expression of T effector and Interferon-γ gene signatures while the expression of multiple oncogenes including ACTR3B, ERBB2, AKT2 and SMARCD1 was down-regulated. Our findings may thus be helpful in guiding further development of immunotherapies for the different subsets of Chinese DLBCL patients.

Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening.

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

[Predictive value of endometrial receptivity and pregnancy outcome by hysteroscopy examination at the phase of implantation window in unexplained infertile women].

OBJECTIVE: To explore predictive value of endometrial receptivity and pregnancy outcome by hysteroscopy examination at the phase of implantation window in unexplained infertile women. METHODS: From Oct. 2007 to Mar. 2009, 93 unexplained infertile women underwent hysteroscopy examination at 7 approximately 9 days after a spontaneous ovulation in Family Planning Research Institute of Guangdong Province. According to the endometrial glandular openings and vascular shape, 79 cases without pathological endometrial changes were divided into 60 cases in good endometrium group and 19 cases in poor endometrium group. The following clinical parameters were analyzed and compared between two groups, including endometrial configuration, thickness, secretion, the development and number of pinopodes, vascular distribution, and the level of sex hormone, leukemia inhibitory factor (LIF) and glycodelin in the uterine flushing, and pregnancy outcome. RESULTS: (1) There was no statistical difference in the level of serum estrogen and progesterone at the phase of implantation window, which were (518 +/- 176) pmol/L, (40 +/- 20) nmol/L in good group and (513 +/- 244) pmol/L, (37 +/- 19) nmol/L in poor group (P < 0.05). The endometrium thickness at periovulatroy and implantation window days (1.06 +/- 0.10) cm/(1.16 +/- 0.08) cm in good group did not show significant difference with (0.93 +/- 0.12) cm/(1.02 +/- 0.10) cm in poor group (P > 0.05). The proportion of type A, B and C endometrium at periovulatory days were 63% (12/19), 37% (7/19) and 0 (0/19) in good group and 23% (14/60), 77% (46/60) and 0 (0/60) in poor group. When compared with those of type A or B between two groups respectively, it all showed statistical difference (P < 0.05). However, at phase of implantation window, endometrium configurations were all type B at both groups. (2) 90% (17/19) of women in good group and 7% (4/60) of women in poor group showed normal endometrial secretion function, which showed significant differences (P < 0.01). (3) The percentage of fully developed pinopodes and abundant pinopodes [84% (16/19) and 90% (17/19)] in good group were significantly higher than 42% (25/60) and 57% (34/60) in poor group (P < 0.05). (4) The level of CD(34) expression and microvessel density [MVD; (40.1 +/- 1.2) positive unit (PU) and (21.7 +/- 4.0)/high power field (HP)] in good group were significantly higher than (18.1 +/- 1.3) PU and (8.5 +/- 1.3)/HP in poor group (P < 0.01). (5) The level of LIF and glycodelin in uterine flushing [(72 +/- 54) ng/L and (196 +/- 20) microg/L] in good group were significantly higher than (15 +/- 16) ng/L and (116 +/- 26) microg/L in poor group (P < 0.05). (6) The rate of clinical pregnancy, spontaneous abortion and term delivery were 74% (14/19), 0 (0/14) and 100% (14/14) in good group and 23% (14/60), 14% (2/14) and 86% (12/14) in poor group, the rate of clinical pregnancy and term delivery in good group were significantly increased when compared with those in poor group (P < 0.01). CONCLUSIONS: Hysteroscopy examination at the phase of implantation window could reflect the development of glandular openings and vasculature. It is a preferable method to evaluate the endometrial receptivity and predict pregnancy outcome.

[Development of reversible oviductal polyethylene contraceptive plugs].

An introduction of the design, features and contraceptive principle of an oviduct contraceptive plug is given in this paper. The plug is made of polyethylene, based on the oviductal morphology. It can be introduced and removed by a hysteroscope and is expected to be a transcervical, implantable and permanent intratubal contraceptive device.