Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials
Abstract
:1. Introduction
2. Results
2.1. Magnitude of Anti-Telomerase (hTERT)-Specific T Helper 1 (TH1) Response was Increased in SCCA Patients Following DCF Chemotherapy
2.2. Peripheral Antigen-Specific T Cells Are Correlated with SCCA Patients’ Survival
2.3. Influence of Peripheral Monocytic Myeloid-Derived Suppressive Cells (M-MDSC) and Regulatory CD4+ T-Cells (Treg) on the Clinical Outcomes of SCCA Patients
2.4. DCF Chemotherapy Alleviated M-MDSC Suppression of hTERT TH1 Immunity
3. Discussion
4. Methods
4.1. Study Design and Participants
4.2. Synthetic Peptides
4.3. Assessment of Antigen Specific T-Cell Responses in Healthy Donors and SCCA Patients
4.4. ELISpot Assay
4.5. Flow Cytometry
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Overall Population n = 82 | HPV Non Responders n = 47 | HPV Responders n = 35 | p-Value * | hTERT Non Responders n = 55 | hTERT Responders n = 27 | p-Value ** | |
---|---|---|---|---|---|---|---|
Genre | |||||||
Female | 63 (76.8%) | 37 (78.7%) | 26 (74.3%) | 0.64 | 42 (76.4%) | 21 (77.8%) | 0.88 |
Male | 19 (23.2%) | 10 (21.3%) | 9 (25.7%) | 13 (23.6%) | 6 (22.2%) | ||
Age | |||||||
Median [IQR] | 60.0 [38.6–84.0] | 59.4 [38.6–78.4] | 61.7 [41.1–84.0] | 0.27 | 60.1 [38.6–84.0] | 59.5 [44.2–78.4] | 0.81 |
ECOG | |||||||
0 | 53 (64.6%) | 31 (66.0%) | 22 (62.9%) | 0.89 | 36 (65.4%) | 17 (63.0%) | 0.87 |
1 | 28 (34.2%) | 15 (31.9%) | 13 (37.1%) | 18 (32.7%) | 10 (37.0%) | ||
2 | 1 (1.2%) | 1 (2.1%) | 0 (0.0%) | 1 (1.8%) | 0 (0.0%) | ||
HIV positif | |||||||
Positive | 78 (95.1%) | 44 (93.6%) | 34 (97.1%) | 0.63 | 52 (94.5%) | 26 (96.3%) | 1.0 |
Negative | 4 (4.9%) | 3 (6.4%) | 1 (2.9%) | 3 (5.6%) | 1 (3.7%) | ||
Stage | |||||||
Locally advanced | 17 (20.7%) | 10 (21.3%) | 7 (20.0%) | 0.71 | 12 (21.8%) | 5 (18.5%) | 0.34 |
Synchronous metastases | 22 (26.8%) | 11 (23.4%) | 11 (31.4%) | 12 (21.8%) | 10 (37.0%) | ||
Metachronous metastases | 43 (52.4%) | 26 (55.3%) | 17 (48.6%) | 31 (56.4%) | 12 (44.4%) | ||
Number of sites involved | |||||||
Median [IQR] | 2.0 [1.0–8.0] | 2.0 [1.0–8.0] | 2.0 [1.0–5.0] | 0.84 | 2.0 [1.0–8.0] | 2.0 [1.0–5.0] | 0.65 |
Previous Chemoradiotherapy | (n = 48) | (n = 29) | (n = 19) | (n = 36) | (n = 11) | ||
MMC + Cape/5FU | 36 (78.3%) | 22 (75.9%) | 14 (82.3%) | 0.34 | 26 (74.3%) | 10 (90.9%) | 0.38 |
CDDP + 5FU | 6 (13.0%) | 5 (17.2%) | 1 (5.9%) | 6 (17.1%) | 0 (0.0%) | ||
Capecitabine | 1 (2.2%) | 1 (3.4%) | 0 (0.0%) | 1 (2.9%) | 0 (0.0%) | ||
Missing | 2 | 0 | 2 | 1 | 1 | ||
RT without CT | |||||||
No | 73 (93.6%) | 41 (93.2%) | 32 (94.1%) | 1.0 | 51 (96.2%) | 22 (88.0%) | 0.32 |
Yes | 5 (6.4%) | 3 (6.8%) | 2 (5.9%) | 2 (3.8%) | 3 (12.0%) | ||
Missing | 4 | 3 | 1 | 2 | 2 | ||
Absolute lymphocyte count | (n = 59) | (n = 35) | (n = 21) | (n = 37) | (n = 19) | ||
Median [IQR] | 1086.0 [860.0–1700.0] | 1159.0 [875.0–1927.0] | 1019.0 [850.0–1411.0] | 0.28 | 1159.0 [820.0–1869.0] | 1019.0 [875.0–1600.0] | 0.56 |
Immune checkpoints expression on CD4 T-cells | |||||||
OX40 | 14.5 [9.6–24.1] | 13.7 [7.4–20.8] | 17.6 [9.5–26.7] | 0.27 | 13.2 [7.9–23.3] | 17.6 [9.5–26.6] | 0.35 |
CD226+ TIGIT− | 34.1 [24.1–44.3] | 32.8 [23.9–42.8] | 35.0 [24.1–44.8] | 0.79 | 34.4 [24.2–42.4] | 31.5 [23.6–45.1] | 0.81 |
CD226+ TIGIT+ | 12.2 [7.9–17.0] | 11.5 [7.8–15.8] | 14.5 [8.8–18.9] | 0.12 | 12.1 [7.9–13.2] | 14.2 [7.4–20.6] | 0.36 |
CD226− TIGIT+ | 8.1 [5.6–10.6] | 7.8 [5.4–9.8] | 8.3 [6.4–11.3] | 0.27 | 8.1 [5.6–10.8] | 7.7 [6.4–10.1] | 0.93 |
PD-1 | 8.6 [6.0–13.0] | 8.9 [5.8–14.2] | 8.9 [6.7–12.3] | 0.79 | 9.4 [6.1–13.5] | 8.1 [5.0–11.8] | 0.37 |
Missing | 0 | 1 | 1 | 1 | 1 | ||
Immune checkpoints expression on CD8 T-cells | |||||||
4-1BB | 0.1 [0.0–0.3] | 0.1 [0.0–0.4] | 0.1 [0.0–0.2] | 0.41 | 0.1 [0.0–0.4] | 0.1 [0.0–0.2] | 0.18 |
CD226+ TIGIT− | 36.6 [22.0–49.1] | 39.3 [23.0–47.3] | 35.9 [21.0–52.4] | 0.82 | 39.7 [23.3–54.2] | 27.4 [21.0–42.4] | 0.05 |
CD226+ TIGIT+ | 17.6 [10.4–27.5] | 17.8 [10.3–26.3] | 16.1 [10.3–24.6] | 0.71 | 14.7 [8.7–28.6] | 17.2 [14.0–29.4] | 0.24 |
CD226− TIGIT+ | 15.9 [9.5–28.8] | 14.7 [9.3–28.0] | 19.0 [10.7–28.8] | 0.28 | 16.3 [9.6–23.0] | 19.3 [12.9–34.4] | 0.06 |
PD-1 | 5.0 [3.3–8.7] | 5.3 [3.8–9.4] | 4.8 [2.6–7.9] | 0.12 | 5.0 [3.6–8.8] | 5.1 [2.9–8.9] | 0.83 |
Missing | 0 | 1 | 1 | 1 | 1 | 1 |
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Spehner, L.; Kim, S.; Vienot, A.; François, E.; Buecher, B.; Adotevi, O.; Vernerey, D.; Abdeljaoued, S.; Meurisse, A.; Borg, C. Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials. Int. J. Mol. Sci. 2020, 21, 6838. https://doi.org/10.3390/ijms21186838
Spehner L, Kim S, Vienot A, François E, Buecher B, Adotevi O, Vernerey D, Abdeljaoued S, Meurisse A, Borg C. Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials. International Journal of Molecular Sciences. 2020; 21(18):6838. https://doi.org/10.3390/ijms21186838
Chicago/Turabian StyleSpehner, Laurie, Stefano Kim, Angélique Vienot, Eric François, Bruno Buecher, Olivier Adotevi, Dewi Vernerey, Syrine Abdeljaoued, Aurélia Meurisse, and Christophe Borg. 2020. "Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials" International Journal of Molecular Sciences 21, no. 18: 6838. https://doi.org/10.3390/ijms21186838
APA StyleSpehner, L., Kim, S., Vienot, A., François, E., Buecher, B., Adotevi, O., Vernerey, D., Abdeljaoued, S., Meurisse, A., & Borg, C. (2020). Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials. International Journal of Molecular Sciences, 21(18), 6838. https://doi.org/10.3390/ijms21186838