Cited by 432Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines

Open access
Peng, Weiyi, Liu, Chengwen, Xu, Chunyu, Lou, Yanyan, Chen, Jieqing, Yang, Yan, Yagita, Hideo, Overwijk, Willem W. +3 more·2012·Cancer Research

Published version of a preprint

Abstract

Adoptive cell transfer (ACT) is considered a promising modality for cancer treatment, but despite ongoing improvements, many patients do not experience clinical benefits. The tumor microenvironment is an important limiting factor in immunotherapy that has not been addressed fully in ACT treatments. In this study, we report that upregualtion of the immunosuppressive receptor programmed cell death-1 (PD-1) expressed on transferred T cells at the tumor site, in a murine model of ACT, compared with its expression on transferred T cells present in the peripheral blood and spleen. As PD-1 can attenuate T-cell-mediated antitumor responses, we tested whether its blockade with an anti-PD-1 antibody could enhance the antitumor activity of ACT in this model. Cotreatment with both agents increased the number of transferred T cells at the tumor site and also enhanced tumor regressions, compared with treatments with either agent alone. While anti-PD-1 did not reduce the number of immunosuppressive regulatory T cells and myeloid-derived suppressor cells present in tumor-bearing mice, we found that it increased expression of IFN-γ and CXCL10 at the tumor site. Bone marrow-transplant experiments using IFN-γR-/- mice implicated IFN-γ as a crucial nexus for controlling PD-1-mediated tumor infiltration by T cells. Taken together, our results imply that blocking the PD-1 pathway can increase IFN-γ at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-12-1187

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 41 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [4]Laszlo G Radvanyi CB Minying Zhang Priscilla Miller MG Nicholas Papadopoulos Patrick Hwu Adoptive T Cell Therapy for Metastatic Melanoma: The MD Anderson Experience. Journal of Immunotherapy 2010 33 863

Cited by

Sorted by citations

Authors
Peng, W., Liu, C., Xu, C., Lou, Y., Chen, J., Yang, Y., Yagita, H., Overwijk, W. W., Lizée, G., Radvanyi, L., & Hwu, P.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Authors' Affiliations: 1Department of Melanoma Medical Oncology, The Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas; and 2Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
Corresponding author
Hwu, Patrick
Venue
Cancer Research
Published
2012-10-14
Volume
72
Issue
20
Pages
5209-5218
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2116158418
Cited by
432
References
41
Citations by year
2026: 18 · 2025: 25 · 2024: 27 · 2023: 38 · 2022: 47 · 2021: 31 · 2020: 30 · 2019: 40 · 2018: 38 · 2017: 34 · 2016: 33 · 2015: 34 · 2014: 17 · 2013: 18 · 2012: 2
FWCI
11.23
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Japan Society for the Promotion of Science (22240089)
  • National Cancer Institute (R01CA143077, CA 016672, R01CA123182, P01CA128913, R01CA116206, P30CA016672)
  • National Center for Research Resources (UL1RR024148)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
anti-PD-1 therapy, adoptive cell transfer, interferon-gamma, CXCL10, chemokines, tumor microenvironment, regulatory T cells, myeloid-derived suppressor cells, IFN-gamma receptor, antitumor immunity, immune cell trafficking
MeSH terms
Animals, Cell Movement, Interferon-gamma, Mice, Transgenic, Neoplasms, Experimental, T-Lymphocytes, Up-Regulation, Lymphocytes, Tumor-Infiltrating, Chemokines, Adoptive Transfer, Cell Proliferation, Mice, Programmed Cell Death 1 Receptor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review