Immune checkpoint blockade sensitivity and progression-free survival associates with baseline CD8 + T cell clone size and cytotoxicity

2021 ◽  
Vol 6 (64) ◽  
Author(s):  
Robert A. Watson ◽  
Orion Tong ◽  
Rosalin Cooper ◽  
Chelsea A. Taylor ◽  
Piyush K. Sharma ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Cell Clone ◽  
Progression Free Survival ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Clone Size ◽  
Free Survival ◽  
T Cell Clone

scholarly journals B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

2018 ◽  
Author(s):  
Johannes Griss ◽  
Wolfgang Bauer ◽  
Christine Wagner ◽  
Margarita Maurer-Granofszky ◽  
Martin Simon ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Human Melanoma ◽  
Checkpoint Blockade ◽  
Inflammatory Factors ◽  
T Effector Cells

Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Established mechanisms that underlie therapy response and resistance center on anti-tumor T cell responses. Here we show that tumor-associated B cells are vital to tumor associated inflammation. Autologous B cells were directly induced by melanoma conditioned medium, expressed pro- and anti-inflammatory factors, and differentiated towards a plasmablast-like phenotype in vitro. We could identify this phenotype as a distinct cluster of B cells in an independent public single-cell RNA-seq dataset from melanoma tumors. There, plasmablast-like tumor-associated B cells showed expression of CD8+T cell-recruiting chemokines such as CCL3, CCL4, CCL5 and CCL28. Depletion of tumor associated B cells in metastatic melanoma patients by anti-CD20 immunotherapy decreased overall inflammation and CD8+T cell numbers in the human melanoma TME. Conversely, the frequency of plasmablast-like B cells in pretherapy melanoma samples predicted response and survival to immune checkpoint blockade in two independent cohorts. Tumor-associated B cells therefore orchestrate and sustain tumor inflammation, recruit CD8+ T effector cells and may represent a predictor for response and survival to immune checkpoint blockade in human melanoma.

scholarly journals Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients

2018 ◽  
Vol 10 ◽  
pp. 175883401774974 ◽  
Author(s):  
Niki Karachaliou ◽  
Maria Gonzalez-Cao ◽  
Guillermo Crespo ◽  
Ana Drozdowskyj ◽  
Erika Aldeguer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Free Survival ◽  
Melanoma Patients ◽  
Ifn Γ ◽  
Nsclc Patients ◽  
Important Marker

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. Conclusions: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.

scholarly journals Immune-Checkpoint Blockade Opposes CD8+ T-cell Suppression in Human and Murine Cancer

2019 ◽  
Vol 7 (3) ◽  
pp. 510-525 ◽  
Author(s):  
Lukas W. Pfannenstiel ◽  
C. Marcela Diaz-Montero ◽  
Ye F. Tian ◽  
Joseph Scharpf ◽  
Jennifer S. Ko ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
T Cell Suppression ◽  
Cell Suppression

scholarly journals Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade

AIDS ◽  
2020 ◽  
Vol 34 (10) ◽  
pp. 1451-1460 ◽  
Author(s):  
Ivo N. SahBandar ◽  
Glen M. Chew ◽  
Michael J. Corley ◽  
Alina P.S. Pang ◽  
Naoky Tsai ◽  
...  
Keyword(s):  
T Cell ◽  
Microbial Communities ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade
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