TY  - JOUR
A1  - John, Vini
A1  - Kotze, Leigh A.
A1  - Ribechini, Eliana
A1  - Walzl, Gerhard
A1  - Du Plessis, Nelita
A1  - Lutz, Manfred B.
T1  - Caveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected murine monocytic myeloid-derived suppressor cells
JF  - Frontiers in Immunology
N2  - Monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic MDSCs (G-MDSCs) have been found to be massively induced in TB patients as well in murine Mtb infection models. However, the interaction of mycobacteria with MDSCs and its role in TB infection is not well studied. Here, we investigated the role of Cav-1 for MDSCs infected with Mycobacterium bovis Bacille-Calmette-Guerín (BCG). MDSCs that were generated from murine bone marrow (MDSCs) of wild-type (WT) or Cav1\(^{−/−}\) mice upregulated Cav-1, TLR4 and TLR2 expression after BCG infection on the cell surface. However, Cav-1 deficiency resulted in a selective defect of intracellular TLR2 levels predominantly in the M-MDSC subset. Further analysis indicated no difference in the phagocytosis of BCG by M-MDSCs from WT and Cav1\(^{−/−}\) mice or caveosome formation, but a reduced capacity to up-regulate surface markers, to secrete various cytokines, to induce iNOS and NO production required for suppression of T cell proliferation, whereas Arg-1 was not affected. Among the signaling pathways affected by Cav-1 deficiency, we found lower phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Together, our findings implicate that (i) Cav-1 is dispensable for the internalization of BCG, (ii) vesicular TLR2 signaling in M-MDSCs is a major signaling pathway induced by BCG, (iii) vesicular TLR2 signals are controlled by Cav-1, (iv) vesicular TLR2/Cav-1 signaling is required for T cell suppressor functions.
KW  - myeloid-derived suppressor cell (MDSC)
KW  - caveolin-1 (Cav-1)
KW  - TLR2
KW  - TLR4
KW  - BCG
KW  - T cell suppression
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195528
SN  - 1664-3224
VL  - 10
IS  - 2826
ER  - 
TY  - JOUR
A1  - D'Andrea, David
A1  - Soria, Francesco
A1  - Grotenhuis, Anne J.
A1  - Cha, Eugene K.
A1  - Malats, Nuria
A1  - Di Stasi, Savino
A1  - Joniau, Steven
A1  - Cai, Tommaso
A1  - Rhijn, Bas W. G. van
A1  - Irani, Jaques
A1  - Karnes, Jeffrey
A1  - Varkarakis, John
A1  - Baniel, Jack
A1  - Palou, Joan
A1  - Babjuk, Marek
A1  - Spahn, Martin
A1  - Ardelt, Peter
A1  - Colombo, Renzo
A1  - Serretta, Vincenzo
A1  - Dalbagni, Guido
A1  - Gontero, Paolo
A1  - Bartoletti, Riccardo
A1  - Larré, Stephane
A1  - Malmstrom, Per-Uno
A1  - Sylvester, Richard
A1  - Shariat, Shahrokh F.
T1  - Association of patients’ sex with treatment outcomes after intravesical bacillus Calmette–Guérin immunotherapy for T1G3/HG bladder cancer
JF  - World Journal of Urology
N2  - Purpose
To investigate the association of patients’ sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette–Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC).

Materials and methods
We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients’ sex with HG-recurrence and disease progression.

Results
A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01–1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92–1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients’ sex was not associated with recurrence (HR 0.99, 95%CI 0.80–1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78–1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78–1.60, p = 0.55).

Conclusion
Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
KW  - bladder cancer
KW  - BCG
KW  - response
KW  - age
KW  - progression
KW  - recurrence
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-344486
VL  - 39
IS  - 9
ER  -