Computer-aided image analysis (CAI) can help objectively quantify morphologic features of hematoxylin-eosin (HE) histopathology images and provide potentially useful prognostic information on breast cancer. We performed a CAI workflow on 1,150 HE images from 230 patients with invasive ductal carcinoma (IDC) of the breast. We used a pixel-wise support vector machine classifier for tumor nests (TNs)-stroma segmentation, and a marker-controlled watershed algorithm for nuclei segmentation. 730 morphologic parameters were extracted after segmentation, and 12 parameters identified by Kaplan-Meier analysis were significantly associated with 8-year disease free survival (P < 0.05 for all). Moreover, four image features including TNs feature (HR 1.327, 95%CI [1.001 - 1.759], P = 0.049), TNs cell nuclei feature (HR 0.729, 95%CI [0.537 - 0.989], P = 0.042), TNs cell density (HR 1.625, 95%CI [1.177 - 2.244], P = 0.003), and stromal cell structure feature (HR 1.596, 95%CI [1.142 - 2.229], P = 0.006) were identified by multivariate Cox proportional hazards model to be new independent prognostic factors. The results indicated that CAI can assist the pathologist in extracting prognostic information from HE histopathology images for IDC. The TNs feature, TNs cell nuclei feature, TNs cell density, and stromal cell structure feature could be new prognostic factors.

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Purpose Tumor infiltrating lymphocytes (TILs) have been extensively described in anti-tumor immunity, but their functional alterations in the immunoediting processes during neoplastic progression in the uterine cervix are still not clear. Our aim was to gain insight into cervical tissue T cell populations, determine if there are any differences in the localization and quantity distribution of T lymphocytes, and to evaluate their role in disease regression or progression in the cervical neoplastic milieu. Patients and methods Serial section analysis of immunohistochemically stained CD4 and CD8 lymphocytes was performed on a total number of 72 samples, categorized into four cohorts: 23 HPV non-infected (HPV-) normal cervix, 20 HPV infected (HPV+) normal cervix, 17 HPV+ low grade cervical intraepithelial neoplasia (CIN), and 12 HPV+ high grade CIN. Results Low infiltrating lymphocytes (ILs) in normal cervix and high ILs in CIN were observed, while the trend of ILs increased with increasing grade of CIN, which was statistically significant ( P <0.0001). Quantitative and localization analysis between the subsets of T cells showed that, in the epithelial layer, infiltrating CD8+ lymphocytes (CD8+ ILs ) were significantly higher than CD4+ ILs in HPV+ normal cervix, while the trend decreased with increasing grade of CIN ( P =0.011). Whereas, in the stromal layer, CD4+ ILs were predominant in all study groups and no statistical difference was found between these groups. However, tumor infiltrating CD8+ lymphocytes (CD8+ TILs ) were noted to be significantly higher than CD4+ TILs in severe dysplastic cases. Conclusion T cell infiltrates were predominant as the grade of the lesion progressed into more advanced lesions, which likely represent the lesions that have persisted over time. The variation in the infiltration rate and the location of CD4+ ILs and CD8 ILs may suggest the efficacious role of CD8 T cells in eliminating HPV infected cervical epithelial cells and also provides insight into the complex role of TILs in facilitating and mediating sustained anti-tumor responses, hence preventing tumor outgrowth.

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Little is known on the immune response after neoadjuvant chemotherapy (NACT) in gastric cancer (GC). The present study aimed to investigate the effects of NACT on tumor cells and tumor-infiltrating lymphocytes (TILs) in patients with GC. Expressions of CD4+ and CD8+ TILs and identified co-inhibitory B7-H4 molecule were examined by immunohistochemical staining in GC tissues of 56 patients who received NACT (NACT group) and 46 patients who did not receive NACT (nNACT group). These markers, clinicopathological features, and overall survival (OS) time between both groups were compared. Results showed that the clinicopathological features of patients were not significantly associated with NACT (P > 0.05), but the rate of low expression of B7-H4 (78.6 vs. 47.8 %, P = 0.005) and rate of high expression of CD4+ TILs (58.9 vs. 39.1 %, P = 0.048) and CD8+ TILs (92.9 vs. 56.5 %, P < 0.001) were both significantly higher in NACT group than that in nNACT group. Further, Kaplan-Meier analysis indicated that there was no significant difference in OS time between the groups. However, in NACT group, those with low B7-H4 expression had significantly longer OS (P = 0.031). The study findings suggest that low expression of B7-H4 could serve as a candidate biomarker for predicting response to NACT and could provide favorable prognostic information in GC.