Pancreatic stellate cells: Partners in crime with pancreatic cancer cells

Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy

: Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy

Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable 3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th–25th percentile) and low (3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules