Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients

Background: While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. Methods: We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy. Using a panel of ~ 40 surface and intracellular markers, we performed in-depth phenotypic and functional immune profiling to identify potential predictive biomarker candidates. Results: Immune profiling of baseline peripheral blood samples using CyTOF revealed that anti-CTLA-4 and anti-PD-1 therapies have distinct sets of candidate biomarkers. The distribution of CD4+ and CD8+ memory/non-memory cells and other memory subsets was different between responders and non-responders to anti-CTLA-4 therapy. In anti-PD-1 (but not anti-CTLA-4) treated patients, we discovered differences in CD69 and MIP-1β expressing NK cells between responders and non-responders. Finally, multivariate analysis was used to develop a model for the prediction of response. Conclusions: Our results indicate that anti-CTLA-4 and anti-PD-1 have distinct predictive biomarker candidates. CD4+ and CD8+ memory T cell subsets play an important role in response to anti-CTLA-4, and are potential biomarker candidates. For anti-PD-1 therapy, NK cell subsets (but not memory T cell subsets) correlated with clinical response to therapy. These functionally active NK cell subsets likely play a critical role in the anti-tumor response triggered by anti-PD-1. Electronic supplementary material The online version of this article (10.1186/s40425-018-0328-8) contains supplementary material, which is available to authorized users

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention

Antepipona assmanni nov.sp. und Antepipona aubrechti nov.sp., zwei neue Arten aus Kenia (Hymenoptera: Vespidae: Eumeninae)

Gusenleitner, J., Gusenleitner, F. (2010): Antepipona assmanni nov.sp. und Antepipona aubrechti nov.sp., zwei neue Arten aus Kenia (Hymenoptera: Vespidae: Eumeninae). Linzer biologische Beiträge 42 (1): 711-72

Chronologisch geordnetes Verzeichnis der Publikationen 586b (2004) bis 650 (2009) von Horst Aspöck

Gusenleitner, F. (2009): Chronologisch geordnetes Verzeichnis der Publikationen 586b (2004) bis 650 (2009) von Horst Aspöck. Linzer biologische Beiträge 41 (1): 973-99

Dr. Josef Gusenleitner zum 80er - ein Leben den Vespiden gewidmet

Gusenleitner, F. (2009): Dr. Josef Gusenleitner zum 80er - ein Leben den Vespiden gewidmet. Linzer biologische Beiträge 41 (2): 1001-105

Dokumente zum wissenschaftlichen Opus von Horst Aspöck für die Periode 2004 bis 2014 anlässlich seines 75. Geburtstags

Gusenleitner, F. (2014): Dokumente zum wissenschaftlichen Opus von Horst Aspöck für die Periode 2004 bis 2014 anlässlich seines 75. Geburtstags. Linzer biologische Beiträge 46 (2): 1843-188

Abb. 1-6 in Beitrag zur Kenntnis der Stelis-Arten Spaniens (Hymenoptera, Apidae, Megachilinae)

Abb. 1-6: (1-3) Stelis hispanica HT: (1) Clypeus-Gestaltung, (2) Form und Skulptur des Scheitels, (3) Bildung der Wangen; (4-6) Stelis annulata: (4) Clypeus-Gestaltung, (5) Bildung des Scheitels, (6) Form und Skulptur der Wangen.Published as part of <i>Schwarz, M. & Gusenleitner, F., 2010, Beitrag zur Kenntnis der Stelis-Arten Spaniens (Hymenoptera, Apidae, Megachilinae), pp. 1311-1321 in Linzer biologische Beiträge 42 (2)</i> on page 1315, DOI: <a href="http://zenodo.org/record/10106167">10.5281/zenodo.10106167</a&gt

Abb. 7-12 in Beitrag zur Kenntnis der Stelis-Arten Spaniens (Hymenoptera, Apidae, Megachilinae)

Abb. 7-12: (7-9) Stelis hispanica HT: (7) Skulptur des Mesonotums, (8) Bildung der Axillen, (9) Gestaltung der Tergite 1 und 2; (10-12) Stelis annulata: (10) Skulptur des Mesonotums, (11) Gestaltung der Axillen, (12) Sternite 1 und 2.Published as part of <i>Schwarz, M. & Gusenleitner, F., 2010, Beitrag zur Kenntnis der Stelis-Arten Spaniens (Hymenoptera, Apidae, Megachilinae), pp. 1311-1321 in Linzer biologische Beiträge 42 (2)</i> on page 1316, DOI: <a href="http://zenodo.org/record/10106167">10.5281/zenodo.10106167</a&gt

Abb. 30-34 in Beitrag zur Kenntnis der Stelis-Arten Spaniens (Hymenoptera, Apidae, Megachilinae)

Abb. 30-34: Stelis ortizi sp.nov.: (30) Gestaltung von Tergit 1, (31) Gestaltung der Tergit 1-4, (32) Skulptur der Tergite 5 und 6, (33), basale Vertiefung von Sternit 2, (34) Skulptur der Sternite.Published as part of <i>Schwarz, M. & Gusenleitner, F., 2010, Beitrag zur Kenntnis der Stelis-Arten Spaniens (Hymenoptera, Apidae, Megachilinae), pp. 1311-1321 in Linzer biologische Beiträge 42 (2)</i> on page 1320, DOI: <a href="http://zenodo.org/record/10106167">10.5281/zenodo.10106167</a&gt