scholarly journals Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

2021 ◽  
Vol 10 (21) ◽  
pp. 5124
Author(s):  
Barbara Link ◽  
Adriana Torres Crigna ◽  
Michael Hölzel ◽  
Frank A. Giordano ◽  
Olga Golubnitschaja
Keyword(s):  
Immune Checkpoint ◽  
Metastatic Cancer ◽  
Palliative Therapy ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Antitumor Effects ◽  
Immunological Activation ◽  
Individual Outcomes ◽  
Abscopal Effects

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and unpredictable. The cases reported so far may nevertheless allow for identifying first biomarkers and clinical patterns. We here review biomarkers that may be helpful to predict the occurrence of abscopal effects and hence to optimize therapy for patients with metastatic cancers.

scholarly journals PD-1/PD-L1 Immune Checkpoint Inhibition with Radiation in Bladder Cancer: In Situ and Abscopal Effects

2019 ◽  
Vol 19 (1) ◽  
pp. 211-220 ◽  
Author(s):  
Alexis Rompré-Brodeur ◽  
Surashri Shinde-Jadhav ◽  
Mina Ayoub ◽  
Ciriaco A. Piccirillo ◽  
Jan Seuntjens ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Abscopal Effects

CXCR1/2 blockade to enhance response to immune checkpoint inhibition in an aggressive orthotopic pancreatic adenocarcinoma model.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 19-19
Author(s):  
Nicholas A. Ullman ◽  
Luis I. Ruffolo ◽  
Katherine M. Jackson ◽  
Alexander Chacon ◽  
Mary Georger ◽  
...  
Keyword(s):  
Triple Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Immune Checkpoint ◽  
Chemokine Receptors ◽  
Therapy Group ◽  
Neutrophil Migration ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

19 Background: Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer related deaths, with the incidence expected to rise in the coming years. Despite conventional chemotherapy and advances in immune checkpoint blockade, 5 year survival remains a dismal 8%. Intratumoral accumulation of granulocytic myeloid derived suppressor cells (G-MDSC) pose a significant barrier to treatment as they contribute to immune evasion by PDAC and correlate with poor prognosis. The ELR+ CXC chemokine receptors CXCR1 and CXCR2 (CXCR1/2) contribute to peripheral neutrophil migration into tissues and have been implicated in tumor mediated G-MDSC recruitment to the tumor microenvironment. Here we present our findings using an orally dosed CXCR1/2 inhibitor, SX-682, in an orthotopic PDAC model. Methods: C57BL/6 mice underwent orthotopic injections with KP2 cells. Mice were randomized into five groups (Table) receiving three weeks of FOLFIRINOX with combinations of SX-682 and/or checkpoint inhibition (anti-PD1/anti-CTLA4). FOLFIRINOX was dosed weekly for three weeks. Checkpoint inhibition was administered twice weekly. Chow weights were monitored for consumption of SX-682. Results: The simultaneous administration of FOLFIRINOX with SX-682 combined with checkpoint inhibition (triple therapy) resulted in a significant increase in survival compared to other groups (p = 0.0001). Notably, there was a significant increase in survival with triple therapy versus FOLFIRINOX plus checkpoint alone (p = 0.0259). Median survival of the triple therapy group was 42.5 days, compared to 37 days with checkpoint inhibition (p = <0.05). There were no differences in chow consumption between the control and medicated chow groups. Conclusions: CXCR1/2 blockade combined with immune checkpoint inhibition and first line chemotherapy significantly enhanced survival in our PDAC mouse model. Thus, CXCR1/2 inhibition with SX-682 represents a promising target for clinical intervention in PDAC. [Table: see text]

scholarly journals Novel Combination Strategies to Enhance Immune Checkpoint Inhibition in Cancer Immunotherapy: A Narrative Review

2020 ◽  
Vol 8 (3) ◽  
pp. 273-280
Author(s):  
Jonathan A. Hermel ◽  
Cassi M. Bruni ◽  
Darren S. Sigal
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Immune Checkpoint ◽  
Nk Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Inkt Cells ◽  
Combination Strategies ◽  
Car T

Programmed cell death protein-1 (PD-1) is an immune checkpoint receptor that induces and maintains tolerance of T cells, invariant natural killer T (iNKT) cells, and natural killer (NK) cells, among other lymphocytes. Immune checkpoint inhibition by PD-1 blockade restores the lymphocytic immunostimulatory phenotype and has been successful in the treatment of various malignancies. However, while immune checkpoint blockade has been shown to provide robust antitumor treatment outcomes, its overall response rate remains low in a significant portion of cancer patients. An essential unmet need in cancer therapy is the development of novel pharmacologic strategies designed to lower rates of resistance associated with immune checkpoint blockade. Therefore, efforts that seek to enhance the efficacy of PD-1 inhibition possess profound immunotherapeutic potential. Here, three promising combination strategies that harness the antitumor effects of immune checkpoint inhibitors (ICIs) together with non-ICI antitumor therapeutic agents are reviewed. These agents include (1) ABX196, a potent inducer of iNKT cells, (2) chimeric antigen receptor (CAR)-T cell therapy, and (3) NK cell therapy. A comprehensive literature search was conducted using the PubMed and ClinicalTrials.gov databases for scientific articles and active trials, respectively, pertaining to immune checkpoint inhibition, iNKT cells, CAR-T cells, and NK cell immunotherapy. Preliminary clinical and preclinical data suggest that these combination treatment regimens greatly suppress tumor growth and may serve as innovative methods to enhance and optimize anticancer immunotherapy.

scholarly journals MP57-11 PD-1/PD-L1 IMMUNE-CHECKPOINT INHIBITION WITH RADIATION IN BLADDER CANCER: IN SITU AND ABSCOPAL EFFECTS

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Alexis Rompré-Brodeur* ◽  
Mina Ayoub ◽  
Surashri Shinde-Jadhav ◽  
Ciriaco Piccirillo ◽  
Jan Seuntjens ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Abscopal Effects

Sinonasal Mucosal Melanoma: A Comparison of Outcomes between Surgical Resection and Immune Checkpoint Inhibition

2020 ◽  
Author(s):  
Shivangi Lohia ◽  
Stephanie Flukes ◽  
Alexander N. Shoushtari ◽  
Akash D. Shah ◽  
Ian Ganly ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Immune Checkpoint ◽  
Mucosal Melanoma ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition
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