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Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways.

Zhang YL, Li J, Mo HY, Qiu F, Zheng LM, Qian CN, Zeng YX - Mol. Cancer (2010)

Bottom Line: The density of CD8+ TIL was positively correlated with lymph node metastasis, while the density of Foxp3+ TIL was negatively associated with T stage (P < 0.05).For survival evaluation, the density of Foxp3+ TIL or Foxp3+ TIL combined with GrB+ TIL together was associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.01) in all patients and in the patients with late-stage diseases (Stages III and IV, P < 0.01).No significant association was found between IL-17+ TIL and clinicopathological characteristic or survival of NPC patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, PR China.

ABSTRACT

Background: Increasing amounts of evidence indicate that tumor infiltrating lymphocytes (TIL) are correlated with the prognosis of cancer patients. This study focuses on the association between the densities of tumor infiltrating cytotoxic T lymphocytes (CTL), activated CTL, regulatory T lymphocytes (Treg) and Th17 lymphocytes, and the prognosis and clinicopathological features of nasopharyngeal carcinoma (NPC) patients.

Results: Double immunohistochemical staining was performed in 106 biopsy specimens from newly diagnosed NPC patients. Prognostic values of infiltrating lymphocyte densities were evaluated by Kaplan-Meier analysis and Cox regression. The density of CD8+ TIL was positively correlated with lymph node metastasis, while the density of Foxp3+ TIL was negatively associated with T stage (P < 0.05). For survival evaluation, the density of Foxp3+ TIL or Foxp3+ TIL combined with GrB+ TIL together was associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.01) in all patients and in the patients with late-stage diseases (Stages III and IV, P < 0.01). Meanwhile a low density of CD8+TIL or high ratio of FOXP3+TIL to CD8+TIL was correlated with better PFS in early stage patients (Stages I and II, P < 0.05). No significant association was found between IL-17+ TIL and clinicopathological characteristic or survival of NPC patients.

Conclusions: Our study identifies for the first time the tumor infiltrating Foxp3+ TIL as an independent favorable factor in the prognosis of NPC patients, especially for the patients with late-stage diseases.

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Related in: MedlinePlus

Results of survival rate with immunohistochemical variables. Individually, the number of Foxp3+ cells (A and D), the ratio of CD8+TIL to Foxp3+ TIL (B and E) and Foxp3 together with GrB+ cells (C and F) are significantly associated with the overall survival (OS, P < 0.005) and progression-free survival (PFS, P < 0.005) in NPC patients.
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Figure 2: Results of survival rate with immunohistochemical variables. Individually, the number of Foxp3+ cells (A and D), the ratio of CD8+TIL to Foxp3+ TIL (B and E) and Foxp3 together with GrB+ cells (C and F) are significantly associated with the overall survival (OS, P < 0.005) and progression-free survival (PFS, P < 0.005) in NPC patients.

Mentions: Of these 106 NPC patients, Kaplan-Meier and log-rank test analyses indicated that the groups with Foxp3+TIL>77.2 cells/HPF (median, n = 53) had a significantly better overall survival (OS, 65 vs. 56 months, median/5 year, P = 0.01) and progression-free survival (PFS, 64 vs. 52 months, median/5 year, P = 0.002) when compared to the groups with Foxp3+TIL = 77.2 cells/HPF (median, n = 53) (Fig 2). However, the number of CD8+, GrB+ or IL-17+ TIL is not significantly associated with OS or PFS (data not shown). Upon univariate analysis, age, sex, LMP1 expression, and densities of CD8+TIL, GrB+TIL and IL-17+TIL showed no prognostic significance for OS and PFS. In contrast, tumor size, lymphoid nodal status, TNM clinical stage and the density of Foxp3+TIL were predictors for OS and PFS (Additional File 2). Furthermore, the multivariate Cox proportional hazards analysis of covariates displayed P < 0.05 in univariate analysis (tumor size, lymphoid nodal status, TNM clinical stage and the number of Foxp3+TIL) indicating that after backward elimination, Foxp3 becomes a strong independent favorable prognostic factor for OS and PFS (P < 0.01, Table 5).


Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways.

Zhang YL, Li J, Mo HY, Qiu F, Zheng LM, Qian CN, Zeng YX - Mol. Cancer (2010)

Results of survival rate with immunohistochemical variables. Individually, the number of Foxp3+ cells (A and D), the ratio of CD8+TIL to Foxp3+ TIL (B and E) and Foxp3 together with GrB+ cells (C and F) are significantly associated with the overall survival (OS, P < 0.005) and progression-free survival (PFS, P < 0.005) in NPC patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2818695&req=5

Figure 2: Results of survival rate with immunohistochemical variables. Individually, the number of Foxp3+ cells (A and D), the ratio of CD8+TIL to Foxp3+ TIL (B and E) and Foxp3 together with GrB+ cells (C and F) are significantly associated with the overall survival (OS, P < 0.005) and progression-free survival (PFS, P < 0.005) in NPC patients.
Mentions: Of these 106 NPC patients, Kaplan-Meier and log-rank test analyses indicated that the groups with Foxp3+TIL>77.2 cells/HPF (median, n = 53) had a significantly better overall survival (OS, 65 vs. 56 months, median/5 year, P = 0.01) and progression-free survival (PFS, 64 vs. 52 months, median/5 year, P = 0.002) when compared to the groups with Foxp3+TIL = 77.2 cells/HPF (median, n = 53) (Fig 2). However, the number of CD8+, GrB+ or IL-17+ TIL is not significantly associated with OS or PFS (data not shown). Upon univariate analysis, age, sex, LMP1 expression, and densities of CD8+TIL, GrB+TIL and IL-17+TIL showed no prognostic significance for OS and PFS. In contrast, tumor size, lymphoid nodal status, TNM clinical stage and the density of Foxp3+TIL were predictors for OS and PFS (Additional File 2). Furthermore, the multivariate Cox proportional hazards analysis of covariates displayed P < 0.05 in univariate analysis (tumor size, lymphoid nodal status, TNM clinical stage and the number of Foxp3+TIL) indicating that after backward elimination, Foxp3 becomes a strong independent favorable prognostic factor for OS and PFS (P < 0.01, Table 5).

Bottom Line: The density of CD8+ TIL was positively correlated with lymph node metastasis, while the density of Foxp3+ TIL was negatively associated with T stage (P < 0.05).For survival evaluation, the density of Foxp3+ TIL or Foxp3+ TIL combined with GrB+ TIL together was associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.01) in all patients and in the patients with late-stage diseases (Stages III and IV, P < 0.01).No significant association was found between IL-17+ TIL and clinicopathological characteristic or survival of NPC patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, PR China.

ABSTRACT

Background: Increasing amounts of evidence indicate that tumor infiltrating lymphocytes (TIL) are correlated with the prognosis of cancer patients. This study focuses on the association between the densities of tumor infiltrating cytotoxic T lymphocytes (CTL), activated CTL, regulatory T lymphocytes (Treg) and Th17 lymphocytes, and the prognosis and clinicopathological features of nasopharyngeal carcinoma (NPC) patients.

Results: Double immunohistochemical staining was performed in 106 biopsy specimens from newly diagnosed NPC patients. Prognostic values of infiltrating lymphocyte densities were evaluated by Kaplan-Meier analysis and Cox regression. The density of CD8+ TIL was positively correlated with lymph node metastasis, while the density of Foxp3+ TIL was negatively associated with T stage (P < 0.05). For survival evaluation, the density of Foxp3+ TIL or Foxp3+ TIL combined with GrB+ TIL together was associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.01) in all patients and in the patients with late-stage diseases (Stages III and IV, P < 0.01). Meanwhile a low density of CD8+TIL or high ratio of FOXP3+TIL to CD8+TIL was correlated with better PFS in early stage patients (Stages I and II, P < 0.05). No significant association was found between IL-17+ TIL and clinicopathological characteristic or survival of NPC patients.

Conclusions: Our study identifies for the first time the tumor infiltrating Foxp3+ TIL as an independent favorable factor in the prognosis of NPC patients, especially for the patients with late-stage diseases.

Show MeSH
Related in: MedlinePlus