Strategies to reinvigorate exhausted CD8+ T cells in tumor microenvironment.

CD8+ T cell exhaustion is a stable dysfunctional state driven by chronic antigen stimulation in the tumor microenvironment (TME). Differentiation of exhausted CD8+ T cells (CD8+ TEXs) is accompanied by extensive transcriptional, epigenetic and metabolic reprogramming. CD8+ TEXs are mainly characterized by impaired proliferative and cytotoxic capacity as well as the increased expression of multiple co-inhibitory receptors. Preclinical tumor studies and clinical cohorts have demonstrated that T cell exhaustion is firmly associated with poor clinical outcomes in a variety of cancers. More importantly, CD8+ TEXs are regarded as the main responder to immune checkpoint blockade (ICB). However, to date, a large number of cancer patients have failed to achieve durable responses after ICB. Therefore, improving CD8+ TEXs may be a breakthrough point to reverse the current dilemma of cancer immunotherapy and eliminate cancers. Strategies to reinvigorate CD8+ TEXs in TME mainly include ICB, transcription factor-based therapy, epigenetic therapy, metabolism-based therapy and cytokine therapy, which target on different aspects of exhaustion progression. Each of them has its advantages and application scope. In this review, we mainly focus on the major advances of current strategies to reinvigorate CD8+ TEXs in TME. We summarize their efficacy and mechanisms, identify the promising monotherapy and combined therapy and propose suggestions to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes.

Novel Prognostic Nomogram to Predict Progression-Free Survival of Patients with Hepatocellular Carcinoma After Transarterial Chemoembolization.

Purpose: A retrospective analysis of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) to identify risk factors was conducted, and a novel predictive nomogram model was constructed. Patients and Methods: A total of 346 HCC patients who underwent TACE as initial treatment were retrospectively included, of which 208 were randomly allocated to the derivation cohort and 138 were allocated to the validation cohort. Progression-free survival (PFS) was used as the follow-up endpoint according to mRECIST. Kaplan‒Meier analysis and the Cox regression model screened out some indicators associated with short-term prognosis, and R language was further used to construct a nomogram model. The nomogram was compared with the classical BCLC staging system. Results: The independent predictors affecting PFS in HCC patients undergoing TACE included the following: 1. Baseline indicators: age (P=0.013), albumin-bilirubin (ALBI) grade (grade 2 vs grade 1, P=0.029; grade 3 vs grade 1, P<0.001), and portal vein tumour thrombus (PVTT, P<0.001); 2. Indicators at the 1-month follow-up: Neutrophil To Lymphocyte Ratio (NLR, P=0.032) and changes in alpha-fetoprotein (AFP, P<0.05) and des-γ-carboxy prothrombin (DCP, P<0.001); and 3. Cumulative treatment numbers of TACE in 6 months (P=0.007). In the derivation cohort, the calibration curve of the nomogram showed a high consistency between the predicted and actual PFS probability, and the nomogram outperformed the BCLC staging system (P=0.004). This result was also confirmed in the validation cohort (P=0.012). Conclusion: The constructed nomogram was suggested to have good predictive efficacy and could be used as a complementary assessment to predict the survival and prognosis of HCC patients treated with TACE.

Infrared Thermal Imaging of Patients With Acute Upper Respiratory Tract Infection: Mixed Methods Analysis.

BACKGROUND: Upper respiratory tract infection is a common disease of the respiratory system. Its incidence is very high, and it can even cause pandemics. Infrared thermal imaging (IRTI) can provide an objective and quantifiable reference for the visual diagnosis of people with acute respiratory tract infection, and it can function as an effective indicator of clinical diagnosis. OBJECTIVE: The aims of this study are to observe and analyze the infrared expression location and characteristics of patients with acute upper respiratory tract infection through IRTI technology and to clearly express the quantification of temperature, analyze the role of IRTI in acute upper respiratory tract diagnostic research, and understand the impact of IRTI in qualitative and quantitative research. METHODS: From December 2018 to February 2019, 154 patients with acute upper respiratory tract infection were randomly selected from the emergency department of the First Affiliated Hospital of Guangzhou Medical University. Among these patients, 73 were men and 81 were women. The subjects were divided into two groups according to the presence of fever, namely, fever and nonfever groups. Qualitative and quantitative analyses of the infrared thermal images were performed to compare the results before and after application of the technology. RESULTS: Using the method described in this paper, through the analysis of experimental data, we elucidated the role of IRTI in the diagnosis of acute upper respiratory tract infection, and we found that qualitative and quantitative IRTI analyses play important roles. Through the combination of theory and experimental data, the IRTI analysis showed good results in identifying acute upper respiratory tract infection. CONCLUSIONS: IRTI technology plays an important role in identifying the infrared expression location and characteristics of patients with acute upper respiratory tract infection as well as in the quantification of clear expression of body temperature, and it provides an objective and quantifiable reference basis for elucidating the pathogenesis of these patients.