Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma

Blair, Alex B.; Li, Zheng

doi:10.21037/cco.2017.06.04

Cited by 14 publications

(9 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vaccines have been designed to generate a humoral/cellular immune response with the aim of stimulating the host immune system to recognize and eliminate tumor cells with specific effector and memory T cells. There are two major categories of tumor vaccines: whole cell vaccines and antigen-specific vaccines ( 289 ). A brief review on the different vaccines currently investigated for pancreatic cancer can be found in the publication by Skelton et al ( 290 ).…”

Section: Other Combination Strategies Exploiting Antigenicity/immunogmentioning

confidence: 99%

“…Preclinical data suggested beneficial effects when two vaccination treatments were co-implemented, e.g., GVAX and CRS-207, a live-attenuated Listeria monocytogenes vaccine expressing the TAA mesothelin, in a sequential combination—a so-called prime/boost approach. The first vaccine was given to initiate or “prime” the immune system, and this immune response was then “boosted” following re-administration of antigen resulting in the induction of a synergistic enhancement of T cell induction and antitumor effect ( 289 ). Based on the preclinical data, a phase II trial (NCT01417000) was conducted resulting in the conclusion that heterologous prime/boost with Cy/GVAX and CRS-207 extended the survival of patients with pancreatic cancer, with minimal toxicity ( 294 ).…”

Section: Other Combination Strategies Exploiting Antigenicity/immunogmentioning

confidence: 99%

See 1 more Smart Citation

Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options

et al. 2018

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC), as the most frequent form of pancreatic malignancy, still is associated with a dismal prognosis. Due to its late detection, most patients are ineligible for surgery, and chemotherapeutic options are limited. Tumor heterogeneity and a characteristic structure with crosstalk between the cancer/malignant cells and an abundant tumor microenvironment (TME) make PDAC a very challenging puzzle to solve. Thus far, targeted therapies have failed to substantially improve the overall survival of PDAC patients. Immune checkpoint inhibition, as an emerging therapeutic option in cancer treatment, shows promising results in different solid tumor types and hematological malignancies. However, PDAC does not respond well to immune checkpoint inhibitors anti-programmed cell death protein 1 (PD-1) or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) alone or in combination. PDAC with its immune-privileged nature, starting from the early pre-neoplastic state, appears to escape from the antitumor immune response unlike other neoplastic entities. Different mechanisms how cancer cells achieve immune-privileged status have been hypothesized. Among them are decreased antigenicity and impaired immunogenicity via both cancer cell-intrinsic mechanisms and an augmented immunosuppressive TME. Here, we seek to shed light on the recent advances in both bench and bedside investigation of immunotherapeutic options for PDAC. Furthermore, we aim to compile recent data about how PDAC adopts immune escape mechanisms, and how these mechanisms might be exploited therapeutically in combination with immune checkpoint inhibitors, such as PD-1 or CTLA-4 antibodies.

show abstract

Section: Other Combination Strategies Exploiting Antigenicity/immunogmentioning

confidence: 99%

Section: Other Combination Strategies Exploiting Antigenicity/immunogmentioning

confidence: 99%

Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Despite numerous methods in PDAC treatment, including new chemotherapeutic agents, emerging immunotherapy, and advanced surgical skills, the long-term survival rate has not shown significant improvement over the past decade. There are few effective therapeutics that can extend the overall survival of patients with PDAC [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

et al. 2018

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a “partner in crime” to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure. In addition to multiple paracrine signaling pathways, recent research has confirmed that PSCs-mediated tumor microenvironment may influence behaviors of PDAC via diverse mechanisms, such as rewiring metabolic networks, suppressing immune responses. These new activities are closely linked with treatment and prognosis of PDAC. In this review, we discuss the recent advances regarding new functions of activated PSCs, including PSCs-cancer cells interaction, mechanisms involved in immunosuppressive regulation, and metabolic reprogramming. It’s clear that these updated experimental or clinical studies of PSCs may provide a promising approach for PDAC treatment in the near future.

show abstract

“…Unfortunately, PDAC represents an immune quiescent, so-called "cold" tumor that is not sensitive to immune checkpoint inhibitors (1). Therefore, PDAC also serves as an ideal model for studying how to overcome the resistance to immune checkpoint inhibitor treatment (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

IDO1 inhibition potentiates vaccine-induced immunity against pancreatic adenocarcinoma

Blair

Kleponis

Thomas

et al. 2019

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma

Cited by 14 publications

References 61 publications

Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options

Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

IDO1 inhibition potentiates vaccine-induced immunity against pancreatic adenocarcinoma

Contact Info

Product

Resources

About