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57 (95%CI 0.39-0.70), volumetric similarity coefficient of 0.74 (0.48-0.89), and Hausdorff distance of 5.23 mm (3.17-9.32 mm). Discrepancy of volume estimate between MRI and TTSB was increasing with tumor size. Discrepancy was significantly different between tumors with a Gleason score 3 + 4 vs. higher grade tumors (0.66 ml vs. 0.78 ml; p = 0.007). There were no significant differences between T2, ADC, and DCE segmentations. CONCLUSIONS We found at best moderate interreader agreement of manual prostate cancer segmentation in mpMRI. Additionally, our study suggests a systematic discrepancy between the tumor volume estimate by MRI segmentation and TTSB core length, especially for large and high-grade tumors. KEY POINTS • Manual prostate cancer segmentation in mpMRI shows moderate interreader agreement. • There are no significant differences between T2, ADC, and DCE segmentation agreements. • There is a systematic difference between volume estimates derived from biopsy and MRI.HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma-adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15-3.15) and adjacent non-neoplastic epithelium (n = 152, p  less then  0.001, HR 2.7, 95% CI 1.59-4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279-10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32-19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p  less then  0.01) and stroma (p  less then  0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p  less then  0.001) and stroma (p  less then  0.01). HLA-DR expression was lower (p  less then  0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma-adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions.BACKGROUND Adoptive tumor-infiltrating lymphocytes (TIL) therapy and interleukin-2 (IL-2) have been investigated in melanoma. AIM To confirm previously observed preventive effects of TIL + IL2 in a subgroup of patients with relapsing metastatic stage III melanoma. METHODOLOGY Open-label, randomized two-group, multicenter five-year trial in adult stage III melanoma patients with only one invaded lymph node after complete resection. Patients received TIL + IL2 or abstention. selleck products TIL + IL2 was administered within 8 weeks after lymph node resection and 4 weeks after. Disease-free survival was assessed every 2 months up to month 18, every 3 months up to month 36 and every 4 months up to 5 years. A once-a-year follow-up was scheduled beyond the five-year follow-up. Safety was assessed throughout the trial. RESULTS Overall, 49 patients accounted for the modified intent-to-treat and 47 for the PP. Slightly more male than female patients participated; mean age was 57.7 ± 11.4 years in the TIL + IL2 group and 53.5 ± 13.0 years in the abstention group. After 5 years of follow-up, 11/26 patients in the TIL + IL2 group and 13/23 in the abstention group had relapsed. There was no statistical difference between the groups (HR 0.63 CI 95% [0.28-1.41], p = 0.258), nine patients in the TIL + IL2 and 11 in the abstention group died with no significant difference between the two groups (HR 0.65 CI95% [0.27 - 1.59], p = 0.34). Safety was good. CONCLUSION We did not confirm results of a previous trial. However, ulceration of the primary melanoma may be considered predictive of the efficacy of TIL in melanoma in adjuvant setting, in a manner similar to interferon α.PURPOSE Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39+CD8+ T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39+CD8+ T cells and seek a potential therapeutic target in ccRCC. EXPERIMENTAL DESIGN We immunohistochemically evaluated clinical value of CD39+CD8+ T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (n = 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan-Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort. RESULTS We found that accumulation of CD39+CD8+ T cells indicated poor prognosis (p  less then  0.0001) and indicated therapeutic benefit of TKIs therapy (p = 0.015). CD39+CD8+ T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39+CD8+ T cells and Tregs (p = 0.037) and M2-polarized macrophages (p  less then  0.0001). Finally, inhibition of CD39 partially restores the anti-tumor function of CD8+ T cells. CONCLUSIONS High CD39+CD8+ T cells indicated poor prognosis in ccRCC, due to impaired anti-tumor function of CD39+CD8+ T cells and indicated therapeutic benefit of TKIs therapy.
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