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

Double immunohistochemical staining for CD8/Foxp3, Foxp3/GrB and Foxp3/IL-17. A. NPC tumor tissue with numerous CD8+ (red) and Foxp3+ (brown) cells (× 200). B. NPC tumor tissue with numerous Foxp3+ (brown) and GrB+ (red) cells (× 200). C. NPC tumor tissue with numerous Foxp3+ (red) and IL-17+ (brown) cells (× 200). The staining patterns show that CD8 is on the cell membrane, GrB and IL-17 are in the cytoplasm, and Foxp3 is in the nucleus. There are a few CD8+Foxp3+ and Foxp3+GrB+ cells, but no Foxp3+IL-17+ cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Double immunohistochemical staining for CD8/Foxp3, Foxp3/GrB and Foxp3/IL-17. A. NPC tumor tissue with numerous CD8+ (red) and Foxp3+ (brown) cells (× 200). B. NPC tumor tissue with numerous Foxp3+ (brown) and GrB+ (red) cells (× 200). C. NPC tumor tissue with numerous Foxp3+ (red) and IL-17+ (brown) cells (× 200). The staining patterns show that CD8 is on the cell membrane, GrB and IL-17 are in the cytoplasm, and Foxp3 is in the nucleus. There are a few CD8+Foxp3+ and Foxp3+GrB+ cells, but no Foxp3+IL-17+ cells.

Mentions: To characterize the subsets of TIL in NPC tissues, we defined the different lymphocyte subsets by specific antibodies: CD8 for CTL, Granzyme B (GrB) for activated CTL, Foxp3 for Tregs and IL-17 for Th17 cells. The CD8 immunostaining demonstrated cytomembrane staining in a subset of TIL around the tumor nests (Fig 1A). The median number of CD8+ cells was 52.50 ± 4.97 cells/high-power field (HPF) and the range was 0.80-231.30 cells/HPF. GrB immunostaining showed a cytoplasmic pattern (Fig 1B) in a subset of lymphocytes in tumor tissues. The median number of GrB+ cells was 32.45 ± 3.01 cells/HPF, and the range was 0.40-160.60 cells/HPF. Foxp3 immunostaining demonstrated nuclear staining in a subset of lymphocytes around tumor tissues (Fig 1A, B, and 1C). The median number of Foxp3+ cells was 87.23 ± 5.50 cells/HPF, and the range was 5.20-322.80 cells/HPF. IL-17 immunostaining established a cytoplasmic pattern (Fig 1C) in a small subset of lymphocytes around tumor tissues. The median number of IL-17+ cells was 5.60 ± 2.36 cells/HPF and the range was 0.00-150.00 cells/HPF. The CD8/Foxp3 double positive subset (Fig 1A) showed a median number of 0.9 ± 0.16 cells/HPF and a range of 0.00-9.30 cells/HPF in TIL. The Foxp3/GrB double positive subset (Fig 1B) showed a median number of 1.8 ± 0.38 cells/HPF and a range of 0.01-22.80 cells/HPF in TIL (Table 2). By general logical linear regression analysis, no significant correlation was found between the densities of any two types of lymphocytes in the present study.


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)

Double immunohistochemical staining for CD8/Foxp3, Foxp3/GrB and Foxp3/IL-17. A. NPC tumor tissue with numerous CD8+ (red) and Foxp3+ (brown) cells (× 200). B. NPC tumor tissue with numerous Foxp3+ (brown) and GrB+ (red) cells (× 200). C. NPC tumor tissue with numerous Foxp3+ (red) and IL-17+ (brown) cells (× 200). The staining patterns show that CD8 is on the cell membrane, GrB and IL-17 are in the cytoplasm, and Foxp3 is in the nucleus. There are a few CD8+Foxp3+ and Foxp3+GrB+ cells, but no Foxp3+IL-17+ cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Double immunohistochemical staining for CD8/Foxp3, Foxp3/GrB and Foxp3/IL-17. A. NPC tumor tissue with numerous CD8+ (red) and Foxp3+ (brown) cells (× 200). B. NPC tumor tissue with numerous Foxp3+ (brown) and GrB+ (red) cells (× 200). C. NPC tumor tissue with numerous Foxp3+ (red) and IL-17+ (brown) cells (× 200). The staining patterns show that CD8 is on the cell membrane, GrB and IL-17 are in the cytoplasm, and Foxp3 is in the nucleus. There are a few CD8+Foxp3+ and Foxp3+GrB+ cells, but no Foxp3+IL-17+ cells.
Mentions: To characterize the subsets of TIL in NPC tissues, we defined the different lymphocyte subsets by specific antibodies: CD8 for CTL, Granzyme B (GrB) for activated CTL, Foxp3 for Tregs and IL-17 for Th17 cells. The CD8 immunostaining demonstrated cytomembrane staining in a subset of TIL around the tumor nests (Fig 1A). The median number of CD8+ cells was 52.50 ± 4.97 cells/high-power field (HPF) and the range was 0.80-231.30 cells/HPF. GrB immunostaining showed a cytoplasmic pattern (Fig 1B) in a subset of lymphocytes in tumor tissues. The median number of GrB+ cells was 32.45 ± 3.01 cells/HPF, and the range was 0.40-160.60 cells/HPF. Foxp3 immunostaining demonstrated nuclear staining in a subset of lymphocytes around tumor tissues (Fig 1A, B, and 1C). The median number of Foxp3+ cells was 87.23 ± 5.50 cells/HPF, and the range was 5.20-322.80 cells/HPF. IL-17 immunostaining established a cytoplasmic pattern (Fig 1C) in a small subset of lymphocytes around tumor tissues. The median number of IL-17+ cells was 5.60 ± 2.36 cells/HPF and the range was 0.00-150.00 cells/HPF. The CD8/Foxp3 double positive subset (Fig 1A) showed a median number of 0.9 ± 0.16 cells/HPF and a range of 0.00-9.30 cells/HPF in TIL. The Foxp3/GrB double positive subset (Fig 1B) showed a median number of 1.8 ± 0.38 cells/HPF and a range of 0.01-22.80 cells/HPF in TIL (Table 2). By general logical linear regression analysis, no significant correlation was found between the densities of any two types of lymphocytes in the present study.

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