Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3 ⁺ , CD8 ⁺ , FoxP3 ⁺ , CD163 ⁺ , and PD-L1 ⁺ cells using multispectral imaging was performed on sections from 119 patients with HPV ^– OSCC. Expression of β ₂ -microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome. We found that, consistent with previous reports, high numbers of CD8 ⁺ T cells at the invasive margin correlated significantly with prolonged overall survival (OS), while the number of FoxP3 ⁺ or PD-L1 ⁺ cells did not. Compiling the number of FoxP3 ⁺ or PD-L1 ⁺ cells within 30 μm of CD8 ⁺ T cells identified a significant association with a high number of suppressive elements close to CD8 ⁺ T cells and reduced OS. Integrating this information into a cumulative suppression index (CSI) increased correlation with OS. Incorporating tumor expression levels of APM components with CSI further improved prognostic power. This multiparametric immune profiling may be useful for stratifying patients with OSCC for clinical trials.

Changes in the tumor microenvironment and immune surveillance represent crucial hallmarks of various kinds of cancer, including oral squamous cell carcinoma (OSCC), and a close crosstalk of hypoxia regulating genes, an activation of chemokines and immune cells has been described. A review about the pivotal role of HIF-1, its crosstalk to various cornerstones in OSCC tumorigenesis is presented. Hypoxia is a frequent event in OSCC and leads to a reprogramming of the cellular metabolism in order to prevent cell death. Hypoxic OSCC cells induce different adaptive changes such as anaerobic glycolysis, pH stabilisation and alterations of the gene and protein expression profile. This complex metabolic program is orchestrated by the hypoxia inducible factor (HIF)-1, the master regulator of early tumor progression. Hypoxia-dependent and -independent alterations in immune surveillance lead to different immune evasion strategies, which are partially mediated by alterations of the tumor cells, changes in the frequency, activity and repertoire of immune cell infiltrates and of soluble and environmental factors of the tumor micromilieu with consecutive generation of an immune escape phenotype, progression of disease and poor clinical outcome of OSCC patients. This review focusses on the importance of HIF-1 in the adaption and reprogramming of the metabolic system to reduced oxygen values as well as on the role of the tumor microenvironment for evasion of OSCC from immune recognition and destruction.

Hypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma.

The product of the HDMX (or MDM4) gene is structurally related to the MDM2 oncoprotein and is also capable of interacting with the tumor suppressor protein p53. The aim of our study was to determine the amplification status of the HDMX gene and the expression of the HDMX mRNA (particularly that of the HDMX‐S splice variant) in soft‐tissue sarcomas (STS). Patients with STS were evaluated for the status of HDMX gene amplification (n = 66) and HDMX‐S mRNA expression (n = 57) within their tumors. DNA, total RNA and protein were isolated from frozen tumor tissue. We determined that the HDMX‐S splice variant transcript was predominant in a subset (14%) of tumor samples and that its expression was correlated with decreased patient survival (15 vs. 53 months, p < 0.0001, log‐rank test) and with a 17‐fold increased risk of a tumor‐related death (p < 0.0001, multivariate Cox's regression model). The tumors from these patients also expressed elevated levels of HDMX‐S protein. The HDMX gene was amplified in 17% of STSs, and the gene amplification was associated with poor prognosis (RR = 6.5, p < 0.0001). There was no correlation between the HDMX gene amplification and overexpression of the HDMX‐S splice variant. In summary, our data indicate that both the overexpression of the HDMX‐S transcript as well as HDMX gene amplification are important prognostic markers for STS.