scholarly journals Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity

2020 ◽  
Vol 20 (1) ◽  
pp. 173-182
Author(s):  
Sang-In Kim ◽  
Anthony K. Park ◽  
Shyambabu Chaurasiya ◽  
Seonah Kang ◽  
Jianming Lu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Checkpoint Inhibitor ◽  
Antiviral Immunity

scholarly journals Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes

2020 ◽  
Vol 22 (5) ◽  
pp. 1392-1402
Author(s):  
J. L. Goggi ◽  
Y. X. Tan ◽  
S. V. Hartimath ◽  
B. Jieu ◽  
Y. Y. Hwang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Pet Imaging ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Granzyme B ◽  
Cell Populations ◽  
Combination Therapies ◽  
Cancer Phenotypes

Abstract Purpose Immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes. Procedures We have assessed the ability of a fluorine-labelled peptide, [18F]AlF-mNOTA-GZP, targeting granzyme B, to stratify ICI response in two syngeneic models of colon cancer, CT26 and MC38. In vivo tumour uptake of [18F]AlF-mNOTA-GZP following ICI monotherapy, or in combination with PD-1 was characterised and correlated with changes in tumour-associated immune cell populations. Results [18F]AlF-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8+ T cells; however, overall uptake and response to monotherapy or combination therapies was very different in the CT26 and MC38 tumours, likely due to the immunostimulatory environment imbued by the MSI-high phenotype in MC38 tumours. Conclusions [18F]AlF-mNOTA-GZP uptake correlates well with changes in CD8+ T cell populations and is able to stratify tumour response to a range of ICIs administered as monotherapies or in combination. However, tracer uptake can be significantly affected by preexisting phenotypic abnormalities potentially confusing data interpretation.

scholarly journals Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002181
Author(s):  
Erin F Simonds ◽  
Edbert D Lu ◽  
Oscar Badillo ◽  
Shokoufeh Karimi ◽  
Eric V Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Prolonged Survival ◽  
Tumor Associated Macrophages ◽  
The Brain ◽  
Immune Profiling

BackgroundGlioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.MethodsWe used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.ResultsICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.ConclusionsOur data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.

Behavior of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Colon Cancer Patients Undergoing Surgery

2011 ◽  
Vol 31 (6) ◽  
pp. 1095-1104 ◽  
Author(s):  
Ausilia Sellitto ◽  
Gennaro Galizia ◽  
Umberto De Fanis ◽  
Eva Lieto ◽  
Anna Zamboli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Patients

Immune control of cytomegalovirus reactivation in stem cell transplantation

Blood ◽  
2021 ◽  
Author(s):  
Mariapia A Degli-Esposti ◽  
Geoffrey R Hill
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Antiviral Immunity ◽  
Antiviral Drugs ◽  
Viral Reactivation ◽  
High Dose ◽  
Cytomegalovirus Reactivation ◽  
The Impact

The reactivation of viruses from latency after allogeneic stem cell transplantation (SCT) continues to represent a major clinical challenge requiring sophisticated monitoring strategies in the context of prophylactic and/or pre-emptive antiviral drugs that are associated with significant expense, toxicity, and rates of failure. Accumulating evidence has demonstrated the association of polyfunctional virus-specific T-cells with protection from viral reactivation, affirmed by the ability of adoptively transferred virus-specific T-cells to prevent and treat reactivation and disease. The roles of innate cells (NK cells) in early viral surveillance, and dendritic cells in priming of T-cells have also been delineated. Most recently, a role for strain-specific humoral responses in preventing early cytomegalovirus (CMV) reactivation has been demonstrated in preclinical models. Despite these advances, many unknowns remain: what are the critical innate and adaptive responses over time, is the origin (e.g. recipient versus donor) and localization (e.g. in parenchymal tissue versus lymphoid organs) of these responses important, how does GVHD and the prevention/treatment thereof (e.g. high dose steroids) impact the functionality and relevance of a particular immune axis, do the immune parameters that control latency, reactivation and dissemination differ, and what is the impact of new antiviral drugs on the development of enduring antiviral immunity. Thus, whilst antiviral drugs have provided major improvements over the last two decades, understanding the immunological paradigms underpinning protective antiviral immunity after SCT offers the potential to generate non-toxic immune-based therapeutic approaches for lasting protection from viral reactivation.

Abstract LB037:89ZED88082A PET imaging to visualize CD8+T cells in patients with cancer treated with immune checkpoint inhibitor

2021 ◽  
Author(s):  
Laura Kist de Ruijter ◽  
Pim P. van de Donk ◽  
Jahlisa S. Hooiveld-Noeken ◽  
Danique Giesen ◽  
Alexander Ungewickell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Pet Imaging ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Patients With Cancer

scholarly journals β-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy

2017 ◽  
Vol 77 (20) ◽  
pp. 5639-5651 ◽  
Author(s):  
Mark J. Bucsek ◽  
Guanxi Qiao ◽  
Cameron R. MacDonald ◽  
Thejaswini Giridharan ◽  
Lauren Evans ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Adrenergic Signaling ◽  
Checkpoint Inhibitor Therapy

scholarly journals Loss of Fas Expression and Function Is Coupled with Colon Cancer Resistance to Immune Checkpoint Inhibitor Immunotherapy

2018 ◽  
Vol 17 (2) ◽  
pp. 420-430 ◽  
Author(s):  
Wei Xiao ◽  
Mohammed L. Ibrahim ◽  
Priscilla S. Redd ◽  
John D. Klement ◽  
Chunwan Lu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Cancer Resistance ◽  
And Function

scholarly journals Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xi Yang ◽  
Quan Qi ◽  
Yuefen Pan ◽  
Qing Zhou ◽  
Yinhang Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Peripheral Blood ◽  
Strong Correlation ◽  
Tumor Tissue ◽  
Cell Populations

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.

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