Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

Cancer statistics, 2020

(2020) Rebecca L. Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA).

(2020) Margaret A. Tempero et al.   JOURNAL OF CLINICAL ONCOLOGY

B cells and tertiary lymphoid structures promote immunotherapy response

(2020) Beth A. Helmink et al.   NATURE

APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.

(2019) Margaret A. Tempero et al.   JOURNAL OF CLINICAL ONCOLOGY

Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer

(2019) Janet E. Murphy et al.   JAMA Oncology

Tumor-intrinsic PIK3CA represses tumor immunogenicity in a model of pancreatic cancer

(2019) Nithya Sivaram et al.   JOURNAL OF CLINICAL INVESTIGATION

Tumor cell–intrinsic EPHA2 suppresses antitumor immunity by regulating PTGS2 (COX-2)

(2019) Nune Markosyan et al.   JOURNAL OF CLINICAL INVESTIGATION

91O A multi-center phase IIa trial to assess the safety and efficacy of BL-8040 (a CXCR4 inhibitor) in combination with pembrolizumab and chemotherapy in patients with metastatic pancreatic adenocarcinoma (PDAC)

(2019) M Hidalgo et al.   ANNALS OF ONCOLOGY

Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy

(2018) Jinyang Li et al.   IMMUNITY

Multi-omics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers

(2018) Daniel J. McGrail et al.   Nature Communications

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

(2018) Rodabe N. Amaria et al.   NATURE MEDICINE

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

(2018) Stephen J. Schuster et al.   NEW ENGLAND JOURNAL OF MEDICINE

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

(2017) Vinod P. Balachandran et al.   NATURE

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

(2017) Sattva S. Neelapu et al.   NEW ENGLAND JOURNAL OF MEDICINE

Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer

(2017) Julienne L. Carstens et al.   Nature Communications

Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer

(2017) Jung-Eun Jang et al.   Cell Reports

T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma

(2017) Ingunn M. Stromnes et al.   Cancer Immunology Research

The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition

(2016) P. S. Hegde et al.   CLINICAL CANCER RESEARCH

Tertiary lymphoid structures, drivers of the anti-tumor responses in human cancers

(2016) Marie-Caroline Dieu-Nosjean et al.   IMMUNOLOGICAL REVIEWS

Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial

(2016) Timothy M Nywening et al.   LANCET ONCOLOGY

Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy

(2016) Hong Jiang et al.   NATURE MEDICINE

Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages

(2016) Esha Mathew et al.   NEOPLASIA

Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer

(2015) N Hiraoka et al.   BRITISH JOURNAL OF CANCER

Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6Clow F4/80+ Extratumoral Macrophages

(2015) Gregory L. Beatty et al.   GASTROENTEROLOGY

Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer

(2015) Daniel V.T. Catenacci et al.   JOURNAL OF CLINICAL ONCOLOGY

Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

(2015) Richard A Moffitt et al.   NATURE GENETICS

Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity

(2014) Ingunn M Stromnes et al.   GUT

Fibroblast heterogeneity in the cancer wound

(2014) Daniel Öhlund et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Immunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation

(2014) E. R. Lutz et al.   Cancer Immunology Research

Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer

(2013) Y Ino et al.   BRITISH JOURNAL OF CANCER

Inflammatory Monocyte Mobilization Decreases Patient Survival in Pancreatic Cancer: A Role for Targeting the CCL2/CCR2 Axis

(2013) D. E. Sanford et al.   CLINICAL CANCER RESEARCH

Emerging landscape of oncogenic signatures across human cancers

(2013) Giovanni Ciriello et al.   NATURE GENETICS

Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer

(2013) C. Feig et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cancer Genome Landscapes

(2013) B. Vogelstein et al.   SCIENCE

Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels

(2013) Vikash P. Chauhan et al.   Nature Communications

Enzymatic Targeting of the Stroma Ablates Physical Barriers to Treatment of Pancreatic Ductal Adenocarcinoma

(2012) Paolo P. Provenzano et al.   CANCER CELL

Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer

(2012) Lauren J. Bayne et al.   CANCER CELL

Targeting Tumor-Infiltrating Macrophages Decreases Tumor-Initiating Cells, Relieves Immunosuppression, and Improves Chemotherapeutic Responses

(2012) J. B. Mitchem et al.   CANCER RESEARCH

CCR2-Dependent Recruitment of Macrophages by Tumor-Educated Mesenchymal Stromal Cells Promotes Tumor Development and Is Mimicked by TNFα

(2012) Guangwen Ren et al.   Cell Stem Cell

The Pancreas Cancer Microenvironment

(2012) C. Feig et al.   CLINICAL CANCER RESEARCH

Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer

(2012) Michael A Jacobetz et al.   GUT

Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

(2012) Julie R. Brahmer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pancreatic stellate cells: a starring role in normal and diseased pancreas

(2012) Minoti V. Apte et al.   Frontiers in Physiology

Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors

(2011) B. Diop-Frimpong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates

(2010) Julie R. Brahmer et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase 2 Trial of Single Agent Ipilimumab (Anti-CTLA-4) for Locally Advanced or Metastatic Pancreatic Adenocarcinoma

(2010) Richard E. Royal et al.   JOURNAL OF IMMUNOTHERAPY

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

(2010) F. Stephen Hodi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein- 

(2010) M. Kraman et al.   SCIENCE

Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma

(2009) Fei Zhao et al.   IMMUNOLOGY

Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

(2009) K. P. Olive et al.   SCIENCE

Carcinoma-Associated Fibroblast-Like Differentiation of Human Mesenchymal Stem Cells

(2008) P. J. Mishra et al.   CANCER RESEARCH