Significance of intratumoral tertiary lymphoid structure (TLS) as predictictive factors of nivolumab therapy after conversion surgery for unresectable gastric cancer: A retrospective study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 412-412
Author(s):  
Hiroaki Tanaka ◽  
Takuya Mori ◽  
Kenjiro Kimura ◽  
Kazuya Muguruma ◽  
Kosei Hirakawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Advanced Gastric Cancer ◽  
Cytotoxic T Cells ◽  
Palliative Surgery ◽  
Conversion Surgery ◽  
T Cell Infiltration ◽  
Highly Effective ◽  
Before And After ◽  
Unresectable Gastric Cancer

412 Background: Conversion surgery for unresectable advanced gastric cancer has been increasing with the development of chemotherapy. Adjuvant chemotherapy regimens after conversion surgery have not been standardized. The main mechanism of nivolumab is augmentation of antitumor immune response of tumor infiltrating cytotoxic T cells (CTL) to cancer cells, and it has recently been reported that nivolumab therapy before and after chemotherapy is effective in other carcinomas. We previously reported that tertiary lymphoid architecture (TLS) correlates with tumor-infiltrating T cells and is associated with a better prognosis in untreated patients. The purpose of this study was to investigate the relationship between the presence of TLS in the primary tumor and prognosis in patients with gastric cancer who underwent conversion therapy. Methods: We evaluated 52 patients with advanced gastric cancer including 17 patients underwent conversion surgery and 35 patients underwent palliative surgery without prior chemotherapy in our department from 2009 to 2017. The local immune environment and presence of TLS was evaluated by immunohistochemical staining. Results: Intratumoral TLS occurred in 20% of patients with advanced cancer who did not receive chemotherapy before surgery and in 52% of patients who received conversion surgery. And the prognosis of patients with the presence of TLS was better than no TLS. Intratumoral CD8 T-cell infiltration was slightly associated presence of TLS. We had a case in which nivolumab was highly effective and converted to conversion surgery, and a case in which nivolumab was highly effective in patients with recurrence after conversion surgery. TLS was observed in the vicinity of the tumor in these patients. Conclusions: The prognosis was good in the case in which intratumoral TLS was present after conversion surgery. These results suggest that the adjuvant nivolumab therapy may improve the outcome of patients underwent conversion surgery for advanced gastric cancer. These results suggest that peri-tumor TLS is a predictor of nivolumab efficacy in adjuvant therapy after conversion surgery.

Association of tumor infiltrating CD8 positive T cells and PDL-1 expression with survival after conversion surgery for unresectable gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 62-62
Author(s):  
Hiroaki Tanaka ◽  
Junya Nishimura ◽  
Yuichiro Miki ◽  
Tatsuro Tamura ◽  
Kazuya Muguruma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
T Cell ◽  
Cd8 T Cell ◽  
High Expression ◽  
Cell Infiltration ◽  
Conversion Surgery ◽  
T Cell Infiltration ◽  
High Expression Group ◽  
Unresectable Gastric Cancer

62 Background: Conversion surgery after chemotherapy responds to unresectable gastric cancer has long-term prognosis, however, chemotherapy after surgery should also be considered to improve treatment outcome. The effectiveness of immune checkpoint inhibitors for gastric cancer has been proved. In this study, we investigated the association between PDL-1 expression and CD8+ T cell infiltration in the primary tumor and prognosis of patients who underwent conversion surgery after S-1-based multidrug chemotherapy in unresectable gastric cancer. Methods: We evaluated PDL-1 expression and CD8 T cell infiltration by immunohistochemical staining and examined the relationship with prognosis in 90 patients with Stage IV gastric cancer who underwent gastrectomy in our department from 2007 to 2015. Results: 90 cases included 47 cases of palliative resection, 26 cases of CY1P 0cases and 17 cases of conversion surgery. Among Conversion Surgery cases, 11 (65%) patients underwent R0 surgery, and the 5-year survival rate was 66%. The 5-year survival rate of non-curative resected cases was 16%. In immunohistochemical examination, PDL-1 high expression was a poor prognostic factor in palliative surgery and CY1P0 cases. Meanwhile, in the case of Conversion Surgery, the 5-year survival rate was 58%, 32%, 61%, and 30% in the order of PDL-1 high expression group, low expression group, CD8 T cell high infiltration, and low infiltration group, respectively. Prognosis of PDL-1 high expression group and CD8 T cell infiltration group was good. There was no association between curative resection and neither of CD8 T cell infiltration or PDL-1 expression. Conclusions: We found that the prognosis was relatively good in patients where local immune response was enhanced, regardless of R0 excision. Our results suggested that infiltration of CD8 T cells in the primary tumor may be a prognostic predictor, and it is expected to use an immune check point inhibitor after conversion surgery for unresectable gastric cancer.

scholarly journals PD-L1 Expression and CD8+ T Cell Infiltration Predict a Favorable Prognosis in Advanced Gastric Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yangyang Wang ◽  
Chunchao Zhu ◽  
Wei Song ◽  
Jun Li ◽  
Gang Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Advanced Gastric Cancer ◽  
High Density ◽  
Cell Infiltration ◽  
Cox Regression Analysis ◽  
T Cell Infiltration ◽  
Programmed Death ◽  
Significant Difference

Advanced gastric cancer (AGC) has high morbidity and mortality in East Asia, and it is urgent to explore new treatments to improve patient prognosis. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have exhibited remarkable activity in clinical trials and were approved by the FDA for clinical therapy in several types of tumors. Here, we evaluated PD-L1 expression and T cell infiltration in AGC. Positive tumor PD-L1 expression was detected in 171 AGCs (33.60%) out of 509 AGCs. PD-L1 expression was positively correlated with CD8+ T cell infiltration. Then, PD-L1 and CD8A mRNA expression was analyzed using gastric cancer data from the TCGA database, confirming a positive correlation. Patient survival was assessed according to PD-L1 status and the T cell infiltration density. PD-L1 expression and a high density of CD8+ T cells in AGCs were associated with improved prognosis, whereas no significant difference was noted between PD-1 and CD3 expression. In contrast, a high density of FOXP3+ T cells in AGCs indicated a poor prognosis. Multivariate Cox regression analysis revealed that CD8+ T cell density acts as an independent predictor of overall survival (OS) in AGC patients. Taken together, this study further highlights targets for immune checkpoint-based therapy in AGC.

scholarly journals Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jieti Wang ◽  
Ruochen Li ◽  
Yifan Cao ◽  
Yun Gu ◽  
Hanji Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Epstein Barr Virus ◽  
Effector Memory ◽  
Feature Identification ◽  
Barr Virus ◽  
T Cell Infiltration ◽  
Epstein Barr ◽  
Gastric Cancer Patients

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.

High levels of tumor-infiltrating lymphocytes showed better clinical outcomes in FOLFOX-treated gastric cancer patients

2020 ◽  
Vol 21 (11) ◽  
pp. 751-759
Author(s):  
Wei Li ◽  
Weili Wang ◽  
Ping Liao ◽  
Kun Song ◽  
Zhanwei Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Median Number ◽  
Cox Regression Analysis ◽  
T Cell Infiltration ◽  
Gastric Cancer Patients ◽  
Infiltrating Lymphocytes

Background: Tumor-infiltrating lymphocytes (TILs) and postoperative chemotherapeutics interact in the tumor micro-environment. This interaction has not been well investigated in gastric cancer. Materials & methods: A total of 129 patients were divided into high or low TILs based on the median number of positive CD3+ and FoxP3+ T cells, which was assessed by immunocytochemistry. Results: Cox regression analysis showed that the stage III disease with shorter overall survival was significant. The analysis showed that high numbers of CD3+ or FoxP3+ T cells have better clinical outcomes in FOLFOX-treated patients. Conclusion: High CD3+ and FoxP3+ T-cell infiltration was associated with better clinical outcomes in patients with gastric cancer treated with FOLFOX, suggesting TILs incorporated into algorithms to improve the therapeutic efficacy of optimal chemotherapy.

Relevance of peritoneal lavage cytology before and after gastrectomy in CY1 and R1 surgery for primary advanced gastric cancer

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 4198-4198
Author(s):  
O. Kobayashi ◽  
A. Tsuburaya ◽  
T. Yoshikawa ◽  
T. Osaragi ◽  
H. Murakami ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Peritoneal Lavage ◽  
Peritoneal Lavage Cytology ◽  
Before And After ◽  
Lavage Cytology

Phase 1 study of paclitaxel, cisplatin, and 5-fluorouracil (TCF) in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14134-14134
Author(s):  
K. Yokoi ◽  
K. Omura ◽  
M. Hirano ◽  
T. Hara ◽  
Y. Munemoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase 1 ◽  
Fixed Dose ◽  
Clinical Effects ◽  
Prior Chemotherapy Regimen ◽  
Disease Stabilization ◽  
Unresectable Gastric Cancer ◽  
Grade 3 ◽  
Anti Tumor Activity

14134 Background: Paclitaxel is effective against gastric cancer with serosal involvement and/or peritoneal dissemination. Combination of cisplatin and 5-fluorouracil is also active against advanced gastric cancer. Therefore, we designed a phase I trial of a combination of paclitaxel, cisplatin and 5-fluorouracil (TCF) to explore potential synergistic effect. Methods: Eligible patients had metastatic or unresectable gastric cancer with up to 1 prior chemotherapy regimen. The fixed dose of cisplatin 25 mg/m2 and paclitaxel 80 mg/m2 with escalation dose of 5-fluorouracil from 300 mg/m2 to a maximum of 600 mg/m2 on days 1, 8 and 15 of a 28 day schedule were administered. MTD and anti-tumor activity were evaluated. Results: No grade 3 or 4 toxicities at least possibly related to the treatments resulting in DLT were observed on every dose level. The clinical effects were determined in 3 patients with measurable lesions out of 7 cases. There were 2 partial responses, and disease stabilization was seen in one patient. Conclusions: Combination of paclitaxel, cisplatin and 5-fluorouracil (TCF) is considered to be feasible, well tolerated and active in patients with advanced gastric cancer and warrants further examination in a phase II trial. No significant financial relationships to disclose.

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