記述言語：日本語   出版者・発行元：Journal of Immunotherapy  

The current biomarkers for immune checkpoint inhibitor (ICI) therapy have several limitations, and new ones are being explored. Retinoblastoma-binding protein 8 (RBBP8) is associated with tumor-infiltrating immune cells (TIIC) and immune checkpoint molecules. Therefore, RBBP8 may serve as a novel biomarker for ICI therapy. Thus, in this study, we investigated the relationship between RBBP8 expression and the tumor immune environment in 58 patients with pathologic T3-4 gastric cancer who underwent radical gastrectomy. Immunohistochemistry of primary tumor specimens was performed to evaluate RBBP8, TIIC, and programmed cell death ligand 1 expression. Kaplan-Meier survival and prognostic factor analyses were also performed using Cox proportional hazards regression models. Patients were divided into RBBP8 high (HG, n=29) and low (LG, n=29) expression groups, using the median RBBP8 expression as the cutoff. The LG had a significantly worse overall survival rate than the HG (log-rank test, P=0.029). Furthermore, the overall survival rate of patients in LG who were treated with ICI (n=7) was worse than that of those in HG (n=9; log-rank P=0.005). Multivariate analysis identified extensive lymph node metastasis and low RBBP8 expression as independent prognostic factors. The HG and LG showed no significant difference in the number of TIICs; however, there was a difference in the number ratios of CD4+/CD8+ (P=0.012) and CD4+/CD3+ cells (P<0.001). Therefore, RBBP8 expression in patients with advanced gastric cancer is a prognostic marker that affects the proportion of CD4+ T-cell infiltration and may also be a biomarker for predicting ICI treatment response.

DOI： 10.1097/CJI.0000000000000550

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PubMed

記述言語：日本語   出版者・発行元：Cancers  

Background/Objectives: The response rate to immune checkpoint inhibitor (ICI) therapy is limited. Further, there is a need to discover biomarkers to predict therapeutic efficacy. The vascular endothelial growth factor (VEGF) is strongly associated with intra-tumoral immunity; however, its utility as a marker remains unknown. Therefore, our objectives were to examine the isoforms of VEGF and determine whether VEGF levels predict ICI efficacy. Methods: Levels of VEGF isoforms VEGF-A121 and VEGF-A165 were measured in stored serum samples obtained from 30 patients with advanced or recurrent gastric cancer who received nivolumab monotherapy at Kagoshima University Hospital, and the association with prognosis and treatment efficacy was retrospectively analyzed. Results: The serum levels of the total VEGF, VEGF-A121, and VEGF-A165 were not significantly associated with prognosis. However, the ratio of VEGF-A121/VEGF-A165 (VEGF-A121/165) exhibited a statistically significant (p = 0.0088) difference in progression-free survival (PFS) with the low-ratio group having a 67-day prolonged median PFS time. Under univariable analysis, only VEGF-A121/165 values exhibited reduced progression-free survival with statistical significance. When comparing treatment responses in the low (n = 15) and high (n = 15) serum VEGF-A-121/165 groups, RECIST evaluation was 3 to 0 for complete response (CR), 2 to 0 for partial response (PR), 3 to 2 for stable disease (SD), and 3 to 10 for progressive disease (PD). Patients with clinically unsettled PR or SD were classified as non-CR/non-PD (4 vs. 3), with a disease control rate of 80% vs. 33%. Conclusions: The serum VEGF-A121/165 ratio may represent a new, easily measured biomarker for predicting the therapeutic response to ICIs.

DOI： 10.3390/cancers16233958

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PubMed

記述言語：日本語   出版者・発行元：Scandinavian Journal of Gastroenterology  

Purpose: This study aims to investigate changes in the tumor immune environment of patients who underwent therapy with a vascular endothelial growth factor (VEGF) inhibitor for advanced colorectal cancer. Methods: Patients (n = 135) with T3 or T4 colorectal cancer were included in this retrospective study. They were classified as follows: patients who had not received preoperative treatment (UPFRONT group, n = 54), who had received FOLFOX as preoperative chemotherapy (FOLFOX group, n = 55), and who had undergone resection after combination FOLFOX and bevacizumab as unresectable colorectal cancer (B-MAB group, n = 26). The number of cytotoxic T lymphocytes (CTLs), FOXP3⁺ lymphocytes (including regulatory T cells (Tregs)), CD163⁺ monocytes (including M2-type tumor-associated macrophages (TAM-M2 type)), and programmed cell death 1 (PD-1)⁺ lymphocytes was evaluated immunohistochemically in the cancer cell area (CC) and stromal cell area (ST) of surgical specimens, and compared among the three groups. Results: The CTL population did not differ among the three groups in both areas. In the B-MAB group, the numbers of PD-1⁺ cells in the ST, FOXP3⁺ lymphocytes in both areas, and CD163⁺monocytes in the ST was lower than that in the other two groups, and a correlation with the histological therapeutic effect was observed. Conclusions: In advanced colorectal cancer, VEGF inhibitors may decrease the number of PD-1⁺ cells and inhibit the infiltration of FOXP3⁺ lymphocytes and CD163⁺monocytes into the tumor environment.

DOI： 10.1080/00365521.2023.2194011

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PubMed

記述言語：日本語   出版者・発行元：Anticancer research  

BACKGROUND/AIM: The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment. MATERIALS AND METHODS: We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis. RESULTS: An increased number of CD8+ T cells in pancreatic cancer tissue was significantly associated with a better patient prognosis. Additionally, patients with a higher ratio of PD-1 expression to CD8+ T cells had a worse prognosis. We observed no correlation between the Tim-3/Galectin-9 and CD155/TIGIT pathways and patient prognosis. CONCLUSION: Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.

DOI： 10.21873/anticanres.15824

Scopus

PubMed

記述言語：日本語   出版者・発行元：(株)北隆館  

免疫チェックポイント阻害剤の治療効果が認められ、消化器がんでも免疫療法が実臨床で用いられるようになってきた。しかし、膵がんにおいては臨床試験でも他のがん種に比べ十分な効果が得られず、適用が進んでいない。理由として膵がんの微小環境において免疫が著しく不活化されていることが挙げられ、そのため免疫療法の確立が困難であると考えられている。本研究では、膵がん切除標本を用いて免疫環境の解析を行い、微小環境内の免疫を抑制するゲノム、エピゲノムのメカニズムを明らかにし、免疫療法の効果を改善させるための標的分子を同定することで新規の膵がん免疫療法に繋げることを目的としている。(著者抄録)

記述言語：日本語   出版者・発行元：(株)ニュー・サイエンス社  

免疫チェックポイント阻害剤の治療効果が認められ、消化器癌でも免疫療法が実臨床で用いられるようになってきた。しかし、膵癌においては臨床試験でも他の癌種に比べ十分な効果が得られず、適用が進んでいない。理由として膵癌の微小環境において免疫が著しく不活化されていることが挙げられ、そのため免疫療法の確立が困難であると考えられている。本研究では、膵癌切除標本を用いて免疫環境の解析を行い、微小環境内の免疫を抑制するゲノム、エピゲノムのメカニズムを明らかにし、免疫療法の効果を改善させるための標的分子を同定することで新規の膵癌免疫療法に繋げることを目的としている。(著者抄録)