Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report
Abstract
:1. Introduction
2. Patients and Materials
2.1. Cremona Retrospective Cohort
2.2. Immunohistochemical Staining
2.3. Evaluation of Immunohistochemistry
2.3.1. PD-L1 Expression
2.3.2. Tumor-Infiltrating Lymphocyte Density
2.4. MGMT and MIB-1
2.5. p53
2.6. Statistical Analysis
3. Results
3.1. Cremona Retrospective Cohort
3.1.1. Patients
3.1.2. PD-L1 Expression
3.1.3. Tumor-Infiltrating Lymphocytes
3.2. Survival Analyses
3.2.1. Association of Patient and Tumor Features with Survival
3.2.2. Survival Analyses in Relation to PD-L1 or CD3
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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Feature | Primary Tumors | Relapse | Overall |
---|---|---|---|
N. (%) * | N. (%) * | N. (%) * | |
Total number | 58 | 11 | 69 |
Age: median (range) | 66 (41–81) | 57 (45–78) | 64 (41–81) |
Sex | |||
Female | 22 (38) | 6 (55) | 28 (41) |
Male | 36 (62) | 5 (45) | 41 (59) |
Type of resection | |||
Gross total resection | 15 (28) | 3 (43) | 18 (30) |
Subtotal resection | 15 (28) | 1 (14) | 16 (27) |
Partial resection | 23 (43) | 3 (43) | 26 (43) |
N.A. | 5 (-) | 4 (-) | 9 (-) |
Alive at the end of follow up | |||
Yes | 4 (7) | 1 (9) | 5 (7) |
No | 54 (93) | 10 (91) | 64 (93) |
Histotype | |||
Glioblastoma | 56 (97) | 10 (91) | 66 (96) |
Gliosarcoma | 2 (3) | 1 (9) | 3 (4) |
Hemisphere | |||
Right | 32 (55) | 5 (46) | 37 (54) |
Left | 26 (45) | 4 (36) | 30 (43) |
Other ** | 0 (0) | 2 (18) | 2 (3) |
Multifocal | |||
No | 47 (81) | 9 (82) | 56 (81) |
Yes | 11 (19) | 2 (18) | 13 (19) |
IDH1 mutated | 0 (0) | 0 (0) | 0 (0) |
MGMT promoter | |||
Methylated | 21 (38) | 7 (78) | 28 (43) |
Unmethylated | 35 (62) | 2 (22) | 37 (57) |
N.A. | 4 (-) | 2 (-) | 4 (-) |
Mib1: median (range) | 35% (4–80%) | 43% (10–60%) | 35% (4–80%) |
P53 | |||
Negative | 7 (12) | 4 (36) | 11 (16) |
Intermediate | 40 (69) | 4 (36) | 44 (64) |
Positive | 11 (19) | 3 (27) | 14 (20) |
P53 | |||
Wild type | 40 (69) | 4 (36) | 44 (64) |
Mutated | 18 (31) | 7 (64) | 25 (36) |
CD3 | |||
Absent | 10 (17) | 2 (18) | 12 (17) |
Mild | 37 (64) | 7 (64) | 44 (64) |
Moderate/High | 11 (19) | 2 (18) | 13 (19) |
CD3+ TILs count: median (range) | 8 (0–90) | 11 (1–57) | 9 (0–90) |
PD-L1 | |||
<1% | 33 (57) | 8 (73) | 41 (59) |
≥1% | 25 (43) | 3 (27) | 28 (41) |
Variable | Hazard Ratio | 95% Confidence Interval | p-Value * |
---|---|---|---|
Age | 1.121 | 1.029–1.220 | 0.009 |
tt(Age) | 0.963 | 0.927–0.9996 | 0.048 |
Sex | |||
Female | 1 | ||
Male | 0.891 | 0.511–1.554 | 0.685 |
Type of surgery | |||
GTR | 1 | ||
Subtotal | 1.255 | 0.576–2.733 | 0.568 |
Partial | 2.675 | 1.263–5.667 | 0.01 |
Hemisphere | |||
Right | 1 | ||
Left | 0.72 | 0.419–1.235 | 0.233 |
Multifocality | |||
No | 1 | ||
Yes | 0.061 | 0.002–1.492 | 0.086 |
tt(Multifocality) | 5.564 | 1.227–25.23 | 0.026 |
MGMT | |||
Methylated | 1 | ||
Unmethylated | 0.485 | 0.131–1.797 | 0.279 |
tt(MGMT) | 1.868 | 1.009–3.458 | 0.047 |
MIB1 | 0.996 | 0.976–1.016 | 0.674 |
p53 | |||
Wild type | 1 | ||
Mutated | 0.994 | 0.553–1.785 | 0.983 |
PD-L1 | |||
Negative | 1 | ||
Positive | 0.8197 | 0.478–1.407 | 0.471 |
CD3 | |||
<median | 1 | ||
≥median | 0.741 | 0.433–1.268 | 0.274 |
Variable | Hazard Ratio | 95% Confidence Interval | p-Value * |
---|---|---|---|
Age | 1.111 | 1.013–1.219 | 0.025 |
tt(Age) | 0.97 | 0.931–1.010 | 0.143 |
Type of surgery | |||
GTR | 1 | ||
Subtotal | 1.28 | 0.551–2.972 | 0.566 |
Partial | 2.749 | 1.135–6.661 | 0.025 |
Multifocality | |||
No | 1 | ||
Yes | 0.052 | 0.002–1.208 | 0.065 |
tt(Multifocality) | 4.335 | 0.983–19.114 | 0.053 |
MGMT | |||
Methylated | 1 | ||
Unmethylated | 0.652 | 0.158–2.695 | 0.555 |
tt(MGMT) | 1.651 | 0.847–3.218 | 0.141 |
ClinicalTrials.gov Identifier | Treatment | PHASE OF TRIAL | Primary End Point | Summary of Results |
---|---|---|---|---|
NCT02017717 | Nivolumab vs. bevacizumab | III | OS | Median OS 9.5 months vs. 9.8 months |
NCT02617589 | Nivolumab vs. Temozolomide + radiation therapy | III | OS | Median OS 13.4months vs. 14.88 months |
NCT02667587 | Temozolomide + radiation therapy + nivolumab or placebo | III | PFS and OS | No survival advantage over placebo |
NCT03743662 | Nivolumab with radiation therapy and bevacizumab | II | OS | Ongoing study |
NCT02550249 | Neoadjuvant nivolumab | II | Efficacy and safety | Median OS 7.3 months |
NCT04396860 | Lpilimumab and nivolumab + radiation therapy | II/III | PFS and OS | Ongoing study |
NCT04145115 | Lpilimumab + nivolumab | II | ORR | Ongoing study |
NCT02337491 | Pembrolizumab with or without bevacizumab | II | MTD, DLT and PFS | Median OS 8.8 months together vs. 10.3 months for pembrolizumab alone |
NCT02336165 | Durvalumab monotherapy, with bevacizumab or with radiaotherapy | II | OS and PFS | Ongoing study |
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Sobhani, N.; Bouchè, V.; Aldegheri, G.; Rocca, A.; D’Angelo, A.; Giudici, F.; Bottin, C.; Donofrio, C.A.; Pinamonti, M.; Ferrari, B.; et al. Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report. Biomedicines 2023, 11, 311. https://doi.org/10.3390/biomedicines11020311
Sobhani N, Bouchè V, Aldegheri G, Rocca A, D’Angelo A, Giudici F, Bottin C, Donofrio CA, Pinamonti M, Ferrari B, et al. Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report. Biomedicines. 2023; 11(2):311. https://doi.org/10.3390/biomedicines11020311
Chicago/Turabian StyleSobhani, Navid, Victoria Bouchè, Giovanni Aldegheri, Andrea Rocca, Alberto D’Angelo, Fabiola Giudici, Cristina Bottin, Carmine Antonio Donofrio, Maurizio Pinamonti, Benvenuto Ferrari, and et al. 2023. "Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report" Biomedicines 11, no. 2: 311. https://doi.org/10.3390/biomedicines11020311