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To determine the clinical significance of serum soluble (s)PD-1 and sPD-L1 in hepatocellular carcinoma (HCC) received radiotherapy (RT). In cohort 1, 144 HCC patients treated with liver RT were obtained from a prospectively collected database. Blood samples were collected 1 day before and 2 weeks after RT. In cohort 2, formalin-fixed paraffin-embedded samples were obtained from 46 patients with HCC, among whom 23 received preoperative RT and the other 23 received direct surgery. The relationship of sPD-1/sPD-L1 in serum or PD-L1 expression in tumor tissues and clinicopathological features were evaluated. In cohort 1, patients with tumor thrombosis (p = 0.01) and advanced stage (p = 0.00) had significantly higher serum sPD-L1 concentrations. Higher sPD-L1 level was negative predictor of progression-free survival (PFS) (HR = 1.53, p= 0.042). In addition, RT significantly increased the expression of sPD-L1 (p = 0.000), which negatively associated with content of serum CD8+ T cells (R = -0.24, p = 0.033). Moreover, no significant associations were found between clinicopathological features and sPD-1. In cohort 2, we confirmed the phenomenon that RT could increase the expression of PD-L1 in tumor tissues (p = 0.001) and the expression level of PD-L1 in tumor tissues was related to decreased cytotoxic T-cell infiltration and a trend of poor prognosis. High PD-L1 expression was associated with poor prognoses in HCC treated with RT. The increases in PD-L1 induced by RT indicated the combined treatment with RT and immune therapy may be promising strategy for HCC. [ABSTRACT FROM AUTHOR]

Immunotherapy with checkpoint inhibitors (ICI) improved survival in HNSCC. Response rates to ICIs remain low, in part due to lack of effective predictors of response to guide patients' selection. PD-L1, as the only biomarker used in prospective research of ICI in HNSCC has generated inconsistent results. Developments in Precision Oncology in HNSCC brings the prospect for new biomarkers. Tumor mutational burden (TMB) is under investigation in many solid tumors and this study assessed the significance and potential role of TMB and PD-L1 in the immunotherapy of HNSCC. This single institution retrospective review includes HNSCC patients (pts) with tumor tissue evaluated for PD-L1 (IHC 22C3 pharmDx kit) and TMB by FoundationOne. PD-L1 was reported as TPS score (prior to 2018) or CPS score (thereafter). TMB and PD-L1 were analyzed for individual association with demographics, disease characteristics and survival, and with progression free survival (PFS) and response to ICI. Pts tested for TMB (mut/Mb) were grouped as TMB(1-5) and TMB(6+) and pts tested for PD-L1 were grouped as PD-L1(0), PD-L1(1-19) and PD-L1(20+). 139 pts were included, 128 pts had TMB, 95 pts had PD-L1 and 92 pts had both results. TMB(6+) was associated with smoking (p=0.03) and with tumor location, with laryngeal cancer pts having higher TMB (p<0.01) and oropharyngeal cancer pts having lower TMB (p p<0.01). PD-L1 was higher in African Americans (p=0.04), in never smokers (p=0.04) and never drinkers (p=0.01), and in pts with earlier cancer stage (p=0.03) and lower tumor stage (p p<0.01). There was no correlation of TMB or PD-L1 with HPV status. TMB(6+) was associated with improved survival in univariate analysis (p=0.02) and in Cox proportional hazards regression model adjusted for age, tobacco, tumor site, nodal stage, previous chemo/radiotherapy and PD-L1 level (p<0.01). No correlation was found between PD-L1 level and prognosis. There was no correlation between TMB and PD-L1 level. Treatment efficacy with ICI was evaluated in 51 pts, of whom 40 pts had TMB and 36 pts had PD-L1 results. There was significant association of continuous TMB score with PFS (p=0.013) and with response to ICI (mean TMB=11.2 in responders and 4.9 in non-responders; p=0.01). Similarly, in categorical analysis, PFS was 538 days in TMB(6+) and 261 days in TMB(1-5) (p=0.04). There was no association between response to ICI or PFS and PD-L1 analyzed as categorical (p=0.89 and p=0.62) or continuous variable (p=0.99 and p=0.66). Inadequate PD-L1 results in this study could be explained by inconsistence in methods. The association of TMB with prognosis and response to ICI in this study warrants further investigations, and prompts a methodology harmonization effort and advancement of TMB in future prospective studies. The recent availability of circulating TMB makes it a further attractive biomarker. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Cancer Associated Macrophage-Like cells (CAMLs) are a type of circulating stromal cell found in the blood of cancer patients (pts), described as of myeloid origin that represent the inflammatory state of the tumor microenvironment. We have previously reported that in non-small cell lung carcinoma (NSCLC), CAML PD-L1 expression is dynamic and trackable throughout chemoradiation (CRT). However, it is unknown if PD-L1 on CAMLs has clinical utility, particularly in immunotherapy (IMT) efficacy after CRT. We studied stage 3 unresectable NSCLC pts treated with (n = 80) or without (n = 55) IMT agents after CRT to evaluate CAML PD-L1 expression on progression free survival (PFS) & overall survival (OS).Materials/methods: We used 2 sets of IMT treated pts: first set from a single arm phase 2 trial treated with CRT and atezolizumab (atezo) (n = 34) and a second from a multi-year prospective study treated with standard of care CRT with consolidation durvalumab (durva) (n = 46). A control group of CRT alone pts (n = 55) were evaluated during the same period (majority before 2018). In all, 135 pts with pathologically confirmed unresectable stage 3 NSCLC were included. 15mL blood samples were taken at Baseline (BL) & ∼1 month after completion of CRT. Blood was filtered & CAMLs quantified for PD-L1 expression using a binary score (0/1 = low & 2/3 = high), to evaluate PFS & OS hazard ratios (HRs) by censored univariate & multivariate analysis at 24 months.Results: CAMLs were found in 92% of all samples, on average 5.2 CAMLs/15mL. From the available tumor biopsies, > 1% PD-L1 expression using DAKO 22c3 did not predict CRT+IMT (atezo/durva) response (PFS HR 1.4 P = 0.642 & OS HR 1.9 P = 0.293). At BL, high CAML PD-L1 was not associated with PFS in CRT alone (HR 1.5 P = 0.435), CRT+atezo (HR 1.0 P = 0.843), or CRT+durva (HR 1.6 P = 0.6180). After CRT, while high CAML PD-L1 did not predict PFS in CRT alone (HR 1.0 P = 0.925), it was associated with superior PFS in CRT+atezo (HR 2.8 P = 0.046), & CRT+durva (HR 5.2 P = 0.036). For OS, high CAML PD-L1 was not predictive of outcomes in CRT alone (HR 0.8 P = 0.929), but strongly predictive of superior OS for CRT+atezo (HR 4.3 P = 0.036) & CRT+durva (HR 5.9 P = 0.033) groups. Combined (atezo or durva, n = 80), 57% of pts had either maintained high PD-L1 before and after CRT (N = 25) or increased from BL (N = 21). Pts with high PD-L1 post CRT had better outcomes than pts with low expression, PFS HR = 4.1 P < 0.001 and OS HR = 4.7 P < 0.001. This pattern was not seen in pts treated with CRT alone (PFS HR = 1.2 P = 0.763 and OS HR = 0.9 P = 0.977).Conclusion: Our data suggests that in unresectable stage 3 NSCLC, high PD-L1 expression on CAMLs after CRT completion is predictive of superior clinical outcomes in pts treated with IMT, but not in those treated with CRT alone. Prospective validation is needed to confirm these findings. [ABSTRACT FROM AUTHOR]