J Gastric Cancer.  2017 Dec;17(4):384-393. 10.5230/jgc.2017.17.e43.

Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses

Affiliations
  • 1Department of Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea. cairus@yuhs.ac
  • 2Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.
  • 3Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei University Health System, Seoul, Korea.
  • 4Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-(¹â¸F)fluoro-D-glucose (¹â¸F-FDG) positron emission tomography (PET)-computed tomography (CT) (¹â¸F-FDG PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs).
MATERIALS AND METHODS
We retrospectively reviewed 56 patients who underwent ¹â¸F-FDG PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: (10×serum albumin value)+(0.005×peripheral lymphocyte counts). Additionally, the maximum standard uptake value (SUVmax) was calculated to evaluate the metabolic activity of cancer cells.
RESULTS
The SUVmax was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=−0.407; P=0.002). A higher SUVmax showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with SUVmax or TILs. Survival analysis, however, indicated that neither SUVmax nor Foxp3 held prognostic significance.
CONCLUSIONS
FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

Keyword

Fluorodeoxyglucose F18; PET-CT; Tumor infiltrating lymphocytes; Regulatory T-cells; Tumor microenvironment

MeSH Terms

Fluorodeoxyglucose F18
Gastrectomy
Glucose
Granzymes
Humans
Lymphocyte Count
Lymphocytes
Lymphocytes, Tumor-Infiltrating
Metabolism
Nutrition Assessment
Positron-Emission Tomography
Retrospective Studies
Stomach Neoplasms
T-Lymphocytes, Regulatory
Tumor Microenvironment
Fluorodeoxyglucose F18
Glucose
Granzymes

Figure

  • Fig. 1 Representative images of 18F-FDG PET-CT and immunohistochemical staining for TILs. (A) Whole-body 18F-FDG PET image demonstrates increased FDG uptake in stomach. (B, C) Axial CT and fused images indicate primary gastric cancer. (D-H) Immunohistochemical analysis of TILs, including CD3, CD4, CD8, Foxp3, and granzyme B. 18F-FDG = 2-deoxy-2-(18F)fluoro-D-glucose; PET = positron emitting tomography; CT = computed tomography; TIL = tumor infiltrating lymphocyte; CD = cluster of differentiation; Foxp3 = Forkhead box P3.

  • Fig. 2 SUVmax on PET-CT and associated characteristics. (A) Correlation analysis of SUVmax and tumor size. (B) SUVmax in comparison to T classification. (C-H) Correlation analysis of SUVmax and TIL subsets, including CD3, CD4, CD8, Foxp3, and granzyme B. Significant correlation shown only between Foxp3 and SUVmax (R=0.431, P<0.001). SUVmax = maximum standard uptake value; PET = positron emitting tomography; CT = computed tomography; TIL = tumor infiltrating lymphocyte; CD = cluster of differentiation; Foxp3 = Forkhead box P3. *P<0.05.

  • Fig. 3 Foxp3 (+) TILs and associated characteristics. (A) Correlation analysis of tumor size and Foxp3. (B, C) Comparison of Foxp3 according to histologic grade of gastric cancer and T classification. No significant associations among histologic grade and T classification were noted, except between T3 and T4. (D) Correlation analysis of PNI and Foxp3. Foxp3 = Forkhead box P3; TIL = tumor infiltrating lymphocyte; PNI = prognostic nutritional index; AWD = well-differentiated; AMD = moderately differentiated; APD = poorly differentiated. *P<0.05.

  • Fig. 4 Kaplan-Meier analysis according to SUVmax and Foxp3 positivity. (A) OS for the high SUVmax and low SUVmax groups. A median OS of 89 months was recorded in the low SUVmax group. However, a median OS was not defined in the high SUVmax group (P=0.425). (B) OS between high Foxp3 and low Foxp3 groups. The median OS in the low Foxp3 group was 89 months, while the median OS in the high Foxp3 group was undefined (P=0.767). The differences between the groups were calculated using the log-rank test. SUVmax = maximum standard uptake value; Foxp3 = Forkhead box P3; OS = overall survival.


Cited by  1 articles

Biomarkers for Evaluating the Inflammation Status in Patients with Cancer
Ali Guner, Hyoung-Il Kim
J Gastric Cancer. 2019;19(3):254-277.    doi: 10.5230/jgc.2019.19.e29.


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