J Gastric Cancer.  2015 Dec;15(4):223-230. 10.5230/jgc.2015.15.4.223.

Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study

• Lee JY
• Son T
• Cheong JH
• Hyung WJ
• Noh SH
• Kim CB
• Park CG
• Kim HI

• KMID: 2391556
• DOI: http://doi.org/10.5230/jgc.2015.15.4.223

Abstract

PURPOSE
The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer.
MATERIALS AND METHODS
In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B.
RESULTS
The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs.
CONCLUSIONS
Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

Keyword

Adenosine triphosphate; Chemotherapy response assay; Lymphocytes, tumor-infiltrating; Stomach neoplasms; Drug screening assays, antitumor

MeSH Terms

Adenosine
Adenosine Triphosphate
Antibodies
Cell Death
Cisplatin
Doxorubicin
Drug Screening Assays, Antitumor
Drug Therapy
Epirubicin
Etoposide
Fluorouracil
Gastrectomy
Granzymes
Humans
Lymphocytes, Tumor-Infiltrating*
Methotrexate
Mitomycin
Paclitaxel
Pilot Projects*
Stomach Neoplasms*
Adenosine
Adenosine Triphosphate
Antibodies
Cisplatin
Doxorubicin
Epirubicin
Etoposide
Fluorouracil
Granzymes
Methotrexate
Mitomycin
Paclitaxel

Figure

• 

  Fig. 1 Survival analysis according to chemotherapeutic agent choice and tumor infiltrating lymphocytes (TILs). (A) Survival of patients who were treated by 5-fluorouracil (5-FU) (P=0.216). From 15 patients, 10 patients underwent 5-FU adjuvant chemotherapy. According to median cell death rates in adenosine triphosphate-based chemotherapy response assays (ATP-CRAs), patients were grouped as sensitive (n=5) and insensitive (n=5) to 5-FU. (B) Survival of patients who were treated with therapeutic agents as determined by ATP-CRAs (n=2) versus those chosen by a physician (n=8) (P=0.105). (C) Survival of high- (n=5) and low-CD3 (n=5) patients. Of the various TIL subsets examined, only high numbers of CD3 TILs (total T lymphocytes) showed favorable prognosis (P=0.008).

• 

  Fig. 2 Pearson's correlation scatter plots for cell death rates in response to various chemotherapeutic agents in adenosine triphosphate-based chemotherapy response assays and tumor infiltrating lymphocyte subsets for 15 patients. (A) CD4-docetaxel cell death rate (CDR). (B) Granzyme B-5-fluorouracil (5-FU) CDR. (C) Granzyme B-Methotrexate CDR. (D) CD3-5-FU CDR. (E) CD3-cisplatin CDR. For all graphs, each point represents results from a single patient.

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