<scp>PD</scp>‐1 expression on peripheral blood T‐cell subsets correlates with prognosis in non‐small cell lung cancer

Waki, Kayoko; Yamada, Teppei; Yoshiyama, Koichi; Terazaki, Yasuhiro; Sakamoto, Shinjiro; Matsueda, Satoko; Komatsu, Nobukazu; Sugawara, Shunichi; Takamori, Shinzo; Itoh, Kyogo; Yamada, Akira

doi:10.1111/cas.12502

Cited by 66 publications

(59 citation statements)

References 36 publications

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“…Overall survival rates are significantly lower in patients with high B7-H1 expression compared with those with low B7-H1 expression in some tumors (14)(15)(16)(17). Abundant PD-1 on tumor-infiltrating T cells is also associated with poor overall survival (6,18,19). Thus, research on B7-H1-PD-1 interactions in the tumor microenvironment is now focused on a new target for immunotherapy in patients with various types of cancer who show high B7-H1 expression on tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

Ishibashi

Tamura

Sunakawa

et al. 2016

Cancer Immunology Research

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B7 homolog 1 (B7-H1)-expressing myeloma cells not only inhibit myeloma-specific cytotoxic T lymphocytes (CTL), but also confer a proliferative advantage: resistance to antimyeloma chemotherapy. However, it remains unknown whether B7-H1 expressed on myeloma cells induces cellular responses associated with aggressive myeloma behaviors. To address this question, we analyzed the proliferation and drug sensitivity of B7-H1-expressing myeloma cells transfected with B7-H1-specific short-hairpin RNA or treated with programmed cell death (PD)-1-Fc-coupled beads. Knockdown of B7-H1 expression in myeloma cells significantly inhibited cell proliferation and increased apoptosis induced by the chemotherapeutic alkylating agent melphalan, with downregulation of the expression of cell cycle-related genes (CCND3 and CDK6) and antiapoptotic genes (BCL2 and MCL1). B7-H1 molecules thus contributed to myeloma cell-cycle progression and suppression of drug-induced apoptosis. B7-H1-expressing myeloma cells had a higher affinity for PD-1 than for CD80. PD-1-Fc beadtreated myeloma cells also became resistant to apoptosis that was induced by melphalan and the proteasome inhibitor bortezomib. Apoptosis resistance was associated with the PI3K/AKT pathway. Both myeloma cell drug resistance and antiapoptotic responses occurred through the PI3K/AKT signaling pathway, initiated from "reverse" stimulation of B7-H1 by PD-1. Therefore, B7-H1 itself may function as an oncogenic protein in myeloma cells. The interaction between B7-H1 on myeloma cells and PD-1 molecules not only inhibits tumorspecific CTLs but also induces drug resistance in myeloma cells through the PI3K/AKT signaling pathway. These observations provide mechanistic insights into potential immunotherapeutic benefits of blocking the B7-H1-PD-1 pathway.

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Section: Introductionmentioning

confidence: 99%

Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

Ishibashi

Tamura

Sunakawa

et al. 2016

Cancer Immunology Research

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“…Boosting for peptide‐specific IgG responses, which were clearly detectable in all 21 patients, was especially apparent in 63% or 100% of patients after the 1st cycle or 2nd cycle of vaccination, respectively. We have reported that boosting of IgG responses is well correlated with overall survival …”

Section: Discussionmentioning

confidence: 98%

Immunological evaluation of peptide vaccination for cancer patients with the HLA‐A26 allele

et al. 2015

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To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26+/A26+ cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26+ advanced cancer patients because of their safety and higher rates of immunological responses.

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“…PD-1 is expressed in tumor samples and has prognostic value in cancer patients 24–26. Moreover, PD-1 expression in peripheral blood cells increased with tumor stage and correlated with prognosis in various cancer 25,27,28. Thus, we believe that PD-1 expression coupled to medical imaging could impact the way to perform diagnosis and prognosis and to predict therapy outcome in cancer.…”

Section: Introductionmentioning

confidence: 93%

Diagnostic value of PD-1 mRNA expression combined with breast ultrasound in breast cancer patients

Fang

Shao

et al. 2018

TCRM

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IntroductionThis study explored the value of measuring programmed death 1 (PD-1) in peripheral blood, combined with breast ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) classification, for differentiation between benign and malignant breast tumors.Materials and methodsWe enrolled 113 patients with breast cancer and 66 patients with benign breast tumors who were admitted to Hangzhou First People’s Hospital from September 2014 to August 2017. The mRNA level of PD-1 was detected by quantitative real-time polymerase chain reaction.ResultsThe mRNA levels of PD-1 were significantly higher in the peripheral blood of patients with breast cancer than those in patients with benign breast tumors. The diagnostic sensitivity of PD-1 mRNA expression was 0.805, the specificity was 0.788, and the area under the curve (AUC) was 0.848 (P < 0.001); the sensitivity of breast ultrasound-based BI-RADS classification was 0.752, the specificity was 0.909, and the AUC was 0.906 (P < 0.001); and the combined sensitivity, specificity, and AUC of the two assays were 0.920, 0.879, and 0.938, respectively (P < 0.001). Progesterone receptor-positive breast cancer patients exhibited high levels of PD-1 expression (P < 0.001).ConclusionThis study suggests that the measurement of PD-1 combined with breast ultrasound-based BI-RADS classification represents a significant improvement for breast cancer diagnosis compared with diagnoses based on either method alone.

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PD‐1 expression on peripheral blood T‐cell subsets correlates with prognosis in non‐small cell lung cancer

Cited by 66 publications

References 36 publications

Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

Immunological evaluation of peptide vaccination for cancer patients with the HLA‐A26 allele

Diagnostic value of PD-1 mRNA expression combined with breast ultrasound in breast cancer patients

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