Anti-CD8 polyclonal antibody

Background A high density of CD8(+)tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8(+)TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8(+)TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection. Methods Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8(+)cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8(+)TIL density at the 25th percentile (i.e., low = quartile 1). The quartile 1 threshold was chosen through a "minimalp value approach" based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8(+)TIL density groups. Results One hundred and forty-nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow-up time was 8.4 years. High CD8(+)TIL density was associated with improved 5-year overall survival (98% vs. 91%,p = .01) and prostate cancer-specific survival (99% vs. 95%,p = .04) compared with patients with low CD8(+)TIL density. There was a trend toward higher 5-year biochemical recurrence-free survival and metastasis-free survival in the cohort of patients with high CD8(+)TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 andp = .05, respectively). In a multivariate analysis high CD8(+)TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17-0.87; p = .02). In contrast to the prognostic value of CD8(+)TIL density, the CD8(+)cell density in the matched normal prostate tissue was not associated with any clinical outcomes. Conclusion Intratumoral CD8(+)T-cell infiltration in the RP specimen is independently associated with improved survival after RP in this high-risk prostate cancer cohort. Pre-RP immunomodulation that promotes intratumoral CD8(+)cytotoxic T-cell infiltration may be beneficial for this population.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TPS3, TTN, and FATI were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.