Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma

Matsuo, Yoshiki; Kono, Koji; Maruyama, Takanori; Watanabe, Masashi; Kawaguchi, Yoshihiko; Kamimura, Kiyoshi; Fujii, Hideki

doi:10.1038/sj.bjc.6604715

Cited by 74 publications

(82 citation statements)

References 29 publications

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“…Relapse-free survival increased significantly in the MHC class I-positive patients compared to the negative patients in the total patient group and the chemotherapy-only group, but not in the PSK group. PSK, protein-bound polysaccharide K. prognosis have been reported to be correlated in various types of cancer, including breast, lung, renal cell carcinoma and colon cancer (8,9,(17)(18)(19). The present study found that the expression rate of MHC class I in primary gastric cancer lesions was 55%, close to the values that have been reported in other studies (20).…”

Section: Correlation Between Expression Of Mhc Class I and Efficacy Osupporting

confidence: 86%

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Ito

Tanaka

Ohira

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Protein-bound polysaccharide K (PSK) is a glycoprotein that is purified from the mushroom Coriolus versicolor. In Japan, PSK is clinically used in combination with anticancer agents following gastric cancer surgery. Evaluation of the response is difficult, as efficacy is determined via antitumor immunoenhancing effects, and for that reason PSK has not become a standard therapy. The present study evaluated the expression of MHC class I in gastric cancer patients who received PSK postoperative adjuvant immunochemotherapy, and investigated the correlation between MHC class I expression and clinical outcomes. The subjects comprised 349 patients with stage II/III gastric cancer, who had received adjuvant therapy following curative resection between 1995 and 2008. MHC class I expression in the primary lesion was evaluated by immunohistochemical staining. Patients were divided into two treatment groups: one was only administered oral chemotherapy (chemotherapy-only group) and the other was administered chemotherapy plus PSK (PSK group). The clinical outcomes were compared between the two groups. The two groups did not differ in regard to their MHC class I expression. Expression-negative cases demonstrated 3-year recurrence-free survival (RFS) rates of 65% in the PSK group and 47% in the chemotherapy-only group. Therefore, the PSK group revealed a prolonged survival. For the 82 expressionnegative cases with pN2 or greater, the RFS rates were 68% in the PSK group and 28% in the chemotherapy-only group, representing a significant difference. Thus, PSK adjuvant immunochemotherapy may be effective in MHC class I-negative patients, who are in a state of antitumor immunological tolerance, and patients with advanced lymph node metastasis of pN2 or greater. IntroductionIn Japan, adjuvant therapy using S-1 is considered effective for stage II/III gastric cancer. However, postoperative recurrence is observed in 30% of stage III patients, and the efficacy of S-1 monotherapy is marginal (1). Thus, combination of S-1 with various anticancer agents is being tested. Protein-bound polysaccharide K (PSK) is a glycoprotein extracted from the mushroom Coriolus versicolor belonging to the Polyporaceae family (2). Use of this antitumor agent is approved by the Japanese health insurance system, and has been confirmed to prolong survival in gastric cancer patients. PSK is considered to demonstrate not only direct cytocidal activity, but also antitumor immunoenhancing effects (3,4). However, the mechanisms of these effects remain unclear, and in addition, since 1994 no studies have reported any clinical efficacy of PSK against gastric cancer, thus this agent has not been recognized as a standard therapy (5).The fact that hosts become immunocompromised at the time of tumor progression has long been considered to be significant. In particular, decreased expression of MHC class I by the tumor is one mechanism which allows evasion of cytotoxic T lymphocytes (CTLs), which play a central role in tumor immunity (6). This has been reported t...

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Section: Correlation Between Expression Of Mhc Class I and Efficacy Osupporting

confidence: 86%

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Ito

Tanaka

Ohira

et al. 2012

Experimental and Therapeutic Medicine

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“…In both murine models and human studies, the expression of CIITA, MHCI, and/or MHCII molecules can influence antitumor immune responses (41)(42)(43). Consistent with this, the expression of MHCI and/or MHCII molecules on tumor cells has been repeatedly shown to impact prognosis (44)(45)(46). Thus, our data raise the possibility that in addition to targeting the mitogenic and survival signals emanating from the EGFR, EGFRIs may influence the immune response to tumor cells by altering the expression of MHCI and/or MHCII molecules.…”

Section: Discussionmentioning

confidence: 72%

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

Pollack

Sapkota

Cartee

2011

Clinical Cancer Research

142

114

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Purpose: Diverse immune-related effects occur with the use of epidermal growth factor receptor inhibitors (EGFRI). In addition to the cutaneous inflammation induced by EGFRIs, these agents have been associated with the exacerbation of autoimmune skin disease and contact hypersensitivity, antiviral effects, and fatal alveolar damage in the setting of lung transplantation. Because EGFR ligands can modulate MHC class I (MHCI) and II (MHCII) molecule expression, we hypothesized that some of the immune-related effects of EGFRIs are due to direct effects on the expression of MHCI and/or MHCII molecules.Experimental Design: Primary human keratinocytes and a malignant keratinocyte cell line (A431) were treated with EGFRIs alone or prior to IFN-g, a potent inducer of MHCI and MHCII molecule expression. CIITA, MHCI, and MHCII RNA expression was measured using quantitative real-time reverse transcriptase PCR, and cell surface MHCI and MHCII protein expression was measured using flow cytometry. Skin biopsies from patients were analyzed for MHCI and MHCII protein expression before and during therapy with an EGFRI using immunohistochemistry.Results: Both EGFR tyrosine kinase inhibitors and ligand-blocking antibodies (cetuximab) augmented the induction of MHCI and MHCII molecules by IFN-g in primary and malignant human keratinocytes. Unexpectedly, the increase in MHCI protein expression did not require the presence of IFN-g. Consistent with these in vitro findings, skin biopsies from cancer patients exhibited increased epidermal MHCI protein expression during therapy with an EGFRI as well as increases in MHCI and MHCII molecule RNA.Conclusions: These studies suggest that EGFRIs may influence immune/inflammatory responses by directly modulating MHC expression. Clin Cancer Res; 17(13); 4400-13. Ó2011 AACR.

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“…However, the frequency of this downregulation varies significantly between tumor types. It can be as high as 48% in esophageal cancer but only 29% in ovarian cancer (34,35). These findings suggest that MHC downregulation is not the only cause of immune escape by tumors.…”

Section: Mhc Downregulation and The Loss Of Immunogenicitymentioning

confidence: 95%

Dual Faces of IFNγ in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity

Mandai

Hamanishi

Abiko

et al. 2016

Clinical Cancer Research

333

277

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Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma

Cited by 74 publications

References 29 publications

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

Dual Faces of IFNγ in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity

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