Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Treatment
2.3. Immunohistochemistry
2.4. Scoring of Immunohistochemistry
2.5. Histological Evaluation
2.6. DNA Isolation
2.7. HPV DNA Detection
2.8. Statistics
3. Results
3.1. Clinical Parameters
3.2. Morphological Evaluation of Tumor Host Responses
3.3. Five-Year Disease-Specific Survival (DSS) Clinical Variables
3.4. Five-Year DSS by Kaplan–Meier Analyses Studying Dichotomized CD3, Foxp3 or CD68 Positivity
3.5. Five-Year DSS by Cox Multivariate Regression Survival Analyses
3.6. Five-Year DSS Cox Multivariate Regression Analysis by Foxp3 Adjusted by Morphological-Derived Parameters with HPV Adjustment
3.7. Five-Year DSS Cox Stepwise Regression Analysis by Foxp3 TIL Levels, Age of the Patient, T Stage, and Whether HPV- and P16 Tumor Positivity
3.8. Five-Year DSS Cox Multivariate Regression Analysis Versus Treatment Period (RT vs. Surgery + RT)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Tumor HPV (−) | Mono-Variate Cox Regression 5Y DSS Within HPV (−) | Tumor HPV (+) | Mono-Variate Cox Regression 5Y DSS Within HPV (+) |
---|---|---|---|---|
Age in years (Mean ± SD) | 62.1 ± 11.0 | n.s. | 62.1 ± 11.0 | p = 0.005 |
Gender (n; Male/Female) | 63/13 | 65/27 | n.s. | |
Tobacco history 1 (Mean ± SD) | 3.5 ± 0.96 | 0.056 | 2.6 ± 1.36 | n.s. |
T stage 2 T1 T2 T3 T4 | 12 20 24 18 | 0.044 | 14 31 31 16 | n.s. |
N stage 2 N0 N1 N2 N3 | 29 14 25 5 | <0.001 | 18 4 65 5 | n.s. |
M stage 2 M0 M1 | 68 3 | 0.004 | 92 0 | n.a. |
Total patients included | 76 | 92 |
Parameter | T Stage | N Stage | TAM CD68 | TIL CD3 | TIL Foxp3 |
---|---|---|---|---|---|
Tumor HPV (−) patients | |||||
TAM CD68 | −0.22 | 0.07 | |||
TIL CD3 | −0.40 *** | 0.14 | 0.62 *** | ||
TIL Foxp3 | −0.21 | 0.12 | 0.49 *** | 0.65 *** | |
Nucl. Poly # | −0.22 | 0.20 | 0.26 | 0.39 *** | 0.38 ** |
Invasion # | 0.11 | 0.09 | 0.02 | −0.30 * | −0.22 |
Inflammation # | −0.19 | −0.05 | 0.32* | 0.49 *** | 0.57 *** |
Desmoplasia # | 0.31 * | −0.07 | −0.20 | −0.41 *** | −0.43 *** |
Tumor HPV (+) patients | |||||
TAM CD68 | −0.04 | 0.05 | |||
TIL CD3 | −0.16 | −0.01 | 0.28 * | ||
TIL Foxp3 | −0.02 | −0.03 | 0.21 | 0.42 *** | |
Nucl. Poly # | 0.07 | 0.20 | 0.22 | 0.23 * | 0.20 |
Invasion # | 0.18 | −0.19 | −0.16 | −0.08 | 0.04 |
Inflammation # | −0.29 ** | 0.29 ** | 0.21 | 0.22 * | −0.16 |
Desmoplasia # | 0.24 * | −0.12 | −0.25 * | −0.29 ** | 0.04 |
Covariate | Significance | RR | 95% CI for RR | |
---|---|---|---|---|
Lower | Upper | |||
Including gender, TNM stage, HPV status and tobacco history + TIL Foxp3 | ||||
TIL Foxp3 | 0.002 | 0.61 | 0.44 | 0.83 |
Including gender, TNM stage, HPV status and tobacco history + TIL CD3 | ||||
TIL CD3 | 0.460 | 0.80 | 0.44 | 1.45 |
Including gender, TNM stage, HPV status and tobacco history + TAM CD68 | ||||
TAM CD68 | 0.058 | 0.54 | 0.28 | 1.02 |
Parameter | Significance | RR | 95% CI for RR | |
---|---|---|---|---|
Lower | Upper | |||
Tumor HPV (−) status | ||||
Gender | 0.238 | 0.38 | 0.08 | 1.89 |
Age of patient | 0.196 | 1.03 | 0.98 | 1.09 |
T-stage | 0.063 | 1.49 | 0.98 | 2.25 |
N-stage | 0.003 | 1.91 | 1.30 | 2.92 |
M-stage | 0.106 | 4.19 | 0.74 | 23.8 |
Tobacco history | 0.107 | 1.74 | 0.89 | 3.40 |
TIL Foxp3 | 0.047 | 0.59 | 0.35 | 0.99 |
Tumor HPV (+) status | ||||
Gender | 0.980 | 0.99 | 0.29 | 3.38 |
Age of patient | 0.001 | 1.08 | 1.03 | 1.12 |
T-stage | 0.716 | 1.10 | 0.67 | 1.80 |
N-stage | 0.105 | 1.65 | 0.90 | 3.00 |
Tobacco history | 0.303 | 1.24 | 0.83 | 1.85 |
TIL Foxp3 | 0.044 | 0.66 | 0.44 | 0.99 |
Covariate | Sign. | RR | 95% CI for RR | |
---|---|---|---|---|
Lower | Upper | |||
Including patient age, TN-stage, HPV status + shown analysis from levels of TIL Foxp3 and desmoplasia | ||||
TIL Foxp3 | 0.010 | 0.68 | 0.50 | 0.91 |
Desmoplasia | 0.003 | 2.72 | 1.40 | 5.26 |
Including patient age, TN-stage, HPV status + shown analysis from levels of TIL Foxp3 and inflammation | ||||
TIL Foxp3 | 0.003 | 0.63 | 0.46 | 0.86 |
Inflammation | 0.500 | 1.27 | 0.63 | 2.55 |
Including patient age, TN-stage, HPV status + shown analysis from levels of TIL Foxp3 and polymorphism | ||||
TIL Foxp3 | 0.000 | 0.56 | 0.42 | 0.76 |
Nucl. poly | 0.019 | 2.30 | 1.15 | 4.59 |
Including patient age, TN-stage, HPV status + shown analysis from levels of TIL Foxp3 and level of invasion | ||||
TIL Foxp3 | 0.001 | 0.61 | 0.45 | 0.82 |
Invasion | 0.227 | 1.44 | 0.80 | 2.62 |
Covariate | Significance | RR | 95% CI for RR | ||
---|---|---|---|---|---|
Lower | Upper | ||||
Step 1 | Tumor HPV | 0.000 | 0.30 | 0.17 | 0.52 |
Step 2 | Tumor HPV | 0.001 | 0.37 | 0.21 | 0.65 |
TIL Foxp3 | 0.002 | 0.64 | 0.48 | 0.85 | |
Step 3 | Tumor HPV | 0.002 | 0.41 | 0.23 | 0.72 |
Age of patients | 0.028 | 1.03 | 1.00 | 1.06 | |
TIL Foxp3 | 0.001 | 0.612 | 0.46 | 0.82 |
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Ljokjel, B.; Haave, H.; Lybak, S.; Vintermyr, O.K.; Helgeland, L.; Aarstad, H.J. Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma. Cancers 2022, 14, 1508. https://doi.org/10.3390/cancers14061508
Ljokjel B, Haave H, Lybak S, Vintermyr OK, Helgeland L, Aarstad HJ. Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma. Cancers. 2022; 14(6):1508. https://doi.org/10.3390/cancers14061508
Chicago/Turabian StyleLjokjel, Borghild, Hilde Haave, Stein Lybak, Olav Karsten Vintermyr, Lars Helgeland, and Hans Jørgen Aarstad. 2022. "Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma" Cancers 14, no. 6: 1508. https://doi.org/10.3390/cancers14061508