Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer.

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.

Humoral and cellular immune responses to COVID-19 mRNA vaccines in immunosuppressed liver transplant recipients.

BACKGROUND: Liver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear. METHODS: We longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs (n = 44) and LTRs (n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4+ and CD8+ T-cell responses. RESULTS: Here, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4+ T-cell responses. However, spike-specific CD4+ T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8+ T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4+ and CD8+ T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8+ T-cell responses after a third vaccination in HDs or LTRs. CONCLUSIONS: The third mRNA vaccination improves both humoral responses and spike-specific CD4+ T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8+ T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8+ T-cell responses in LTRs and HDs.

People with a liver transplant don't have as strong an immune response to COVID-19 vaccines as healthy people. This study investigates how these individuals produce protective proteins, called antibodies, and CD4 and CD8 T cell immune responses. CD4 T cells are responsible for commanding the immune response and CD8 T cells for remembering and fighting the virus in future. We found that liver transplant recipients have a weaker ability to produce antibodies after vaccination, which is even more noticeable in those taking drugs to prevent transplant rejection. While a third vaccine dose improves their ability to produce antibodies, and to have a CD4 T cell response, it doesn't boost the CD8 T cell response. In summary, an extra vaccine dose can strengthen the immune response in liver transplant recipients but doesn't improve some aspects of their immune memory.

Gaze measurements during viewing human dialogue scenes in adults with ADHD: Preliminary findings.

AIM: Eye gaze measurement to human dialogue scenes in adults with attention deficit hyperactivity disorder (ADHD) was investigated. We examined whether eye gaze measurement might be a biological marker of ADHD. METHODS: Twenty-two individuals with ADHD (mean age, 34.5 years) attending the outpatient clinic of Showa University Karasuyama Hospital were included in the study, and 26 healthy individuals (mean age, 32.6 years) with no history of mental disorders were used as the control group. For the participants, intellectual functioning was estimated using the Japanese Adult Reading Test, and mental symptoms were assessed using the Autism Spectrum Quotient and Conner's Adult ADHD Rating Scale. We extracted human dialogue scenes from two classic movies as visual stimuli and recorded the participant's gaze while watching these scenes using Tobii's eye tracker. RESULTS: For gazing time, repeated measures analysis of variance showed no significant main effect of "group" and no significant interaction effect between "group" and areas of interest "(AOI)." In the normal group, gazing time at the eyes was significantly longer than those at the mouth, body, and background; in the ADHD group, gazing time at the eyes was significantly longer than only that at the background. CONCLUSION: Given the different results obtained in the past in ASD, these results suggest that it would be necessary to directly compare the two groups to determine whether the gaze measurement shows significant differences in ASD and ADHD.

Predictive value of preoperative echocardiographic assessment for postoperative atrial fibrillation after esophagectomy for esophageal cancer.

BACKGROUND: Postoperative atrial fibrillation (POAF) after esophagectomy for esophageal cancer is not uncommon. The aim of this study is to examine whether preoperative transthoracic echocardiography is useful for predicting new-onset POAF in esophageal cancer. METHODS: In this prospective observational study, we evaluated 200 patients with esophageal cancer who underwent esophagectomy at our hospital between January 2016 and July 2019. Conventional echocardiographic assessment and tissue Doppler imaging were performed before surgery. We investigated the utility of preoperative transthoracic echocardiography for predicting new-onset POAF in esophageal cancer. RESULTS: New-onset POAF occurred in 51 (25.5%) of 200 patients. POAF was significantly associated with older age (p = 0.007), higher body mass index (p = 0.020), preoperative hypertensive disease (p = 0.021), and lower hemoglobin level (p = 0.028). The incidence of postoperative complications was significantly higher in patients with POAF than in patients without POAF (43.1% vs. 24.2%, p = 0.013). Transthoracic echocardiography showed that left atrial diameter (LAD) and E wave/e' wave ratio (E/e') were significantly higher in patients with POAF than in patients without POAF (34.1 vs. 31.3 mm, p < 0.001 and 11.6 vs. 10.5, p = 0.003, respectively). Multivariate analysis showed that LAD ≥ 36.0 mm, E/e' ≥ 8.4 are independent risk factors for POAF (odds ratios 2.47 and 3.64; p values 0.035 and 0.027, respectively) CONCLUSIONS: Preoperative echocardiographic evaluation is useful for predicting the onset of POAF after esophagectomy for esophageal cancer. Risk stratification using LAD and E/e' enables clinicians to identify patients at high risk for POAF before esophagectomy.

[Two Cases of Locally Recurrent Rectal Cancer Undergoing Preoperative Chemoradiationtherapy].

Case 1 is a 68-year-old woman with locally recurrent rectal cancer(LRRC)developed 5 years after resection of primary rectal cancer. The tumor seized right lateral side in pelvic. We performed tumor excision after preoperative chemoradiation comprised external beam radiation with oral S-1(tegafur/gimeracil/oteracil). He has been relapse-free for 3 years 3months after surgery. Case 2 is a 74-year-old man with LRRC developed 2 years after resection of primary rectal cancer. The tumor was located dorsal to anastomosis site in pelvic. We performed abdominoperineal resection for LRRC after preoperative chemoradiation with oral S-1. He has been relapse-free for 2 years. It was suggested that preoperative radiotherapy combined with oral FU for local recurrence after rectal cancer may contribute to distant and local control.