Limits...
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.

Show MeSH

Related in: MedlinePlus

Results of survival rate with immunohistochemical variables in different disease stages (n = 39). A. In the early disease stage, the number of CD8+ cells (A and C) and the ratio of CD8+TIL to Foxp3+ TIL (B and D) are significantly associated with PFS (P < 0.05). B. In the late disease stage, the number of Foxp3+ cells (A and C) and Foxp3+ together with GrB+ cells (B and D) are significantly associated with OS (P < 0.01) and PFS (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2818695&req=5

Figure 3: Results of survival rate with immunohistochemical variables in different disease stages (n = 39). A. In the early disease stage, the number of CD8+ cells (A and C) and the ratio of CD8+TIL to Foxp3+ TIL (B and D) are significantly associated with PFS (P < 0.05). B. In the late disease stage, the number of Foxp3+ cells (A and C) and Foxp3+ together with GrB+ cells (B and D) are significantly associated with OS (P < 0.01) and PFS (P < 0.01).

Mentions: To further evaluate the association between different lymphocyte variables and the patient outcome, we classified the patients by their clinical stages: early disease (stages I and II, n = 38) and late disease (stages III and IV, n = 68). We assessed the correlation between the density of CD8, GrB, Foxp3 and IL-17 positive TIL and patient outcome in different disease stages. Our results showed that, in early disease stage patients, a higher number of CD8+TIL was significantly associated with poor PFS (P = 0.025) without significant association with OS. A higher ratio of CD8 to Foxp3 was also found to be significantly associated with poor OS and PFS (P = 0.041 and 0.001, respectively, Fig 3A). However, the aforementioned factors did not significantly impact OS or PFS in late stage patients (data not shown). In contrast, a higher Foxp3+TIL number was significantly associated with a better OS (P = 0.012) and PFS (P = 0.001) in late stage patients (Fig 3B), but had no significant influence on OS and PFS in early stage patients. Additionally, the combination of tumor infiltrating Foxp3+ cells and GrB+ activated CTL was associated with the survival of late stage patients: a higher number of Foxp3+ and GrB+ cells was associated with a longer OS and PFS compared to a lower number of Foxp3+ and GrB+ cells (P < 0.001, Fig 3B).


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 in different disease stages (n = 39). A. In the early disease stage, the number of CD8+ cells (A and C) and the ratio of CD8+TIL to Foxp3+ TIL (B and D) are significantly associated with PFS (P < 0.05). B. In the late disease stage, the number of Foxp3+ cells (A and C) and Foxp3+ together with GrB+ cells (B and D) are significantly associated with OS (P < 0.01) and PFS (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Results of survival rate with immunohistochemical variables in different disease stages (n = 39). A. In the early disease stage, the number of CD8+ cells (A and C) and the ratio of CD8+TIL to Foxp3+ TIL (B and D) are significantly associated with PFS (P < 0.05). B. In the late disease stage, the number of Foxp3+ cells (A and C) and Foxp3+ together with GrB+ cells (B and D) are significantly associated with OS (P < 0.01) and PFS (P < 0.01).
Mentions: To further evaluate the association between different lymphocyte variables and the patient outcome, we classified the patients by their clinical stages: early disease (stages I and II, n = 38) and late disease (stages III and IV, n = 68). We assessed the correlation between the density of CD8, GrB, Foxp3 and IL-17 positive TIL and patient outcome in different disease stages. Our results showed that, in early disease stage patients, a higher number of CD8+TIL was significantly associated with poor PFS (P = 0.025) without significant association with OS. A higher ratio of CD8 to Foxp3 was also found to be significantly associated with poor OS and PFS (P = 0.041 and 0.001, respectively, Fig 3A). However, the aforementioned factors did not significantly impact OS or PFS in late stage patients (data not shown). In contrast, a higher Foxp3+TIL number was significantly associated with a better OS (P = 0.012) and PFS (P = 0.001) in late stage patients (Fig 3B), but had no significant influence on OS and PFS in early stage patients. Additionally, the combination of tumor infiltrating Foxp3+ cells and GrB+ activated CTL was associated with the survival of late stage patients: a higher number of Foxp3+ and GrB+ cells was associated with a longer OS and PFS compared to a lower number of Foxp3+ and GrB+ cells (P < 0.001, Fig 3B).

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