Fen Zhao

CD8+/FOXP3+ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer

Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p < 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p < 0.001). Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC.

FDG-PET Predicts Pain Response and Local Control in Palliative Radiotherapy With or Without Systemic Treatment in Patients With Bone Metastasis From Non–small-cell Lung Cancer

UNLABELLED The purpose of the present study was to evaluate the prognostic value of the maximal standardized uptake value (SUVmax) from serial positron emission tomography scans in patients with bone metastases from non-small-cell lung cancer. The results showed that the pre-RT SUVmax predicted the initial pain severity and local control. Moreover, the change in the SUVmax after palliative radiotherapy predicted the pain response and local control rate. INTRODUCTION We sought to evaluate the value of fluorine-18 fluorodeoxyglucose positron emission tomography (PET) in predicting the pain severity, pain response, and in-field tumor control after palliative radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC) bone metastases. MATERIALS AND METHODS The present retrospective, institutional review board-approved study involved 74 patients with NSCLC and 185 bone metastatic lesions. All patients had undergone PET-computed tomography (CT) scans before and after RT. The pain scores were determined using a numerical rating scale, and the maximal standardized uptake value (SUVmax) at each location was recorded. The pain scores and responses to RT were compared using the pre-RT SUVmax and SUVmax changes after RT. Cox regression analyses were performed to identify the prognostic factors for in-field progression-free survival (PFS) and in-field event-free survival (EFS). RESULTS The pre-RT SUVmax correlated with the initial pain scores (r = 0.885, P < .001), and the decrease in the SUVmax after RT was associated with the pain response to RT (P = .001). During the follow-up period, 47.03% and 38.92% of the lesions showed in-field tumor radiographic progression and in-field events, respectively. The Cox regression analyses showed that a higher pre-RT SUVmax (≥ 8.2) was an independent prognostic factor of worse in-field PFS and worse in-field EFS (hazard ratio [HR] 1.42 and 1.46; P = .044 and P = .005, respectively) and that a greater SUVmax decrease (≥ 28.3%) after RT was an independent prognostic factor of better in-field PFS and better in-field EFS (HR 0.59 and 0.60, respectively; P < .001 for both). CONCLUSION In patients with NSCLC osseous metastasis treated with palliative RT, the pre-RT SUVmax predicted the initial pain severity and local control. Moreover, the change in the SUVmax after RT predicted the pain response and local control.

Current landscape and future directions of biomarkers for predicting responses to immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs), represented by anti-CTLA-4 or anti-PD-1/anti-PD-L1 pathway antibodies, have led to a revolution in cancer treatment modalities. ICIs have unique clinical benefits, such as effectiveness against a broad range of tumor types, strong overall impact on survival, and persistent responses after the cessation of therapy. However, only a subset of patients responds to these therapies, and a small proportion of patients even experience rapid progression or an increased risk of death. Therefore, it is imperative to optimize patient selection for treatment. This review focuses on the mechanisms of tumor escape from immune surveillance, the composition and activity of a preexisting immune infiltrate, the degree of tumor foreignness (as reflected by the mutational burden, expression of viral genes, and driver gene mutations), and host factors (including peripheral blood biomarkers, genetic polymorphisms, and gut microbiome) to summarize current evidence on the biomarkers of responses to ICIs and explore the future prospects in this field.