Table 1.
Summary of retrieved studies investigating the impact of chemo- and radiotherapy on PD-L1 expression in head and neck squamous cell carcinoma.
| Author, Year (Country) | N Cases | Sites | Therapy | Scoring System | Clone | MAIN RESULTS | Potential Limitations |
|---|---|---|---|---|---|---|---|
| Clone E1L3N (6 studies) | |||||||
| Delafoy, 2021 (France) [30] | 44 | HNSCC NOS | Concurrent cisplatin and RT | TC and IC scored separately, positive if >1% | E1L3N | Positivization in TC in the majority of cases where PD-L1 expression changed after therapy, but decrease after radiation | No correspondence between Bx and Rx nor separation of data |
| Doescher, 2020 (Germany) [31] | 67 | HNSCC excluded sinonasal and RP | Concurrent platinum-based CHT and RT | TC and IC scored separately with H-score | E1L3N | No significant changes in the expression of PD-1 on neither tumor nor TIL during therapy | No use of established CPS cutoffs as in trials, small sample size, heterogeneity in tumor locations, fixation and storage of tissue blocks and treatments with no stratification |
| Gomez-Roca, 2020 (France) [32] | 26 | Oral, OP, L, HP | Inhibitor of apoptosis protein Debio 1143 with and without cisplatin | TC and IC as % positive cells | E1L3N | Increased PD-L1 levels in IC with neoadjuvant target therapy with inhibitor of apoptose protein and in combination with cisplatin, but not with cisplatin alone, not in TC | Pharmacodynamic and pharmacogenomic study with no use of established CPS cutoffs as in trials |
| Leduc, 2018 (France) [34] | 21 | Oral and L | Docetaxel, platinum and fluorouracil (TPF) | TC and IC scored separately with >5% as positive | E1L3N | Significant increase of PD-L1 expression in IC and TC after therapy | Small sample size |
| Long, 2021 (China) [37] | 24 | NP | Concurrent IMRT and cisplatin | TPS, positive if >1%, CPS | E1L3N | Different distribution of changes in PD-L1 expression according to score used whether TPS or CPS | Not full correspondence of data in tables and text of the article |
| Ock, 2017 (Korea) [42] | 35 | OP mainly | Docetaxel, platinum and fluorouracil (TPF) regimens or cisplatin-based regimens and concurrent RT | TPS > 5% as positive | E1L3N | Statistically significant up-regulation of PD-L1 in 69% of originally negative cases and upregulation of PD-L1 after radiotherapy | Small sample size, and unclear detailing of IHC protocol |
| Clone SP142 (2 studies) | |||||||
| Chan, 2017 (China) [36] | 161 | NP | IMRT and CHT with cisplatin | TC and IC with cutoff 1% | SP142 | Reduction of PD-L1 expression in 56% cases in IC and in 33% in TC after treatment | No separated data for patients receiving radiotherapy alone |
| So, 2020 (Korea) [43] | 42 | Oral cavity, L, OP, HP, sinuses | RT only | TC and IC positive if >10%, automated scoring on WSI digitized slides | SP142 | Ratio of recurrent (R) vs. initial (I) PD-L1 expression was <1 in 69% cases with TC turning negative in 23% and positive in 9% | Small sample size, retrospective design, and different treatment characteristics among patients |
| Other clones (7 studies, a clone each) | |||||||
| Karabajakian, 2021 (France) [33] | 35 | Oral, OP, HP, L | RT-CHT NOS | CPS | QR1 | Majority of samples positive at CPS1 remained positive (76%), while majority of negative CPS samples at diagnosis became positive at relapse (75%), but change of different entity at different cutoffs CPS1 and CPS20 | No special limitations |
| Naruse, 2020 (Japan) [39] | 121 | Tongue | Platinum-based CHT | TC only, positive if >5% | Abcam ab156361 | No marked difference in expression of PD-L1 in recurrent patients who had surgery alone or CHT plus surgery | No use of CPS or approved assay and no reporting of CI or p values for comparisons; only reporting for correlation with clinicopathological variables and prognosis |
| Ono, 2020 (Japan) [40] | 30 | L, OP, HP | Cisplatin-based RT-CHT | TPS and IC density score | clone D3 | No significant changes in PD-L1 expression after RT-CHT | Small sample size |
| Pflumio, 2021 (France) [35] | 100 | Oral, OP, L, HP | RT-CHT NOS | TPS > 1% | SP263 | Significantly lower percentage of PD-L1+ TC within the irradiated area cohort than the de novo cohort and significantly fewer tumors with PD-L1+ IC in the irradiated area cohort | Indirect comparison, as 50 irradiated cancers are compared with 50 de novo cancers and no CPS used |
| Seki-Soda, 2021 (Japan) [41] | 71 | Oral cavity | Preoperative fluorouracil-based CHT | TC | 28-8 | PD-L1 positivity in TC significantly decreased by CHT irrespective of clinical response | No use of established CPS cutoffs as in trials |
| Shen, 2020 (China) [38] | 47 age 64 y) | HP | Platinum-based CHT and RT | TC | 66248-1-Ig | PD-L1 expression increased after RT | Not stated a clear cutoff for positivity, only 10% for low vs. high |
| Wolf, 2020 (USA) [44] | 96 | Oral cavity | Multi-cytokine preparation with cyclophosphamide | IC and H-score, CPS | Multiplex fluorescence IHC | No significant changes in PD-L1 expression after CHT | Small sample size |
Bx, biopsy specimen; CHT, chemotherapy; CI, confidence interval; CPS, combined positive score; EMT, epithelia-mesenchymal transition; FU, follow-up; HNSCC, head and neck squamous cell carcinoma; HP, hypopharynx; IC, immune cells; IHC, immunohistochemistry; IMRT, intensity modulated radiation therapy; L, laryngeal; M, male; NOS, not otherwise specified; NP, nasopharyngeal; OP, oropharyngeal; OS, overall survival; PFS, progression-free survival; RP, rhinopharynx; RT-CHT, radio-chemotherapy; Rx, resection specimen; TC, tumor cells; TILs, tumor-infiltrating lymphocytes; TPS, tumor proportion score; WSI, whole-slide imaging; y, years.