Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Blood Collection
2.2. Lymphocyte Isolation
2.3. Pre-Existing Immunity Detection and Analysis
2.4. Flow Cytometry Analysis
2.5. Statisical Analysis
3. Results
3.1. Pre-Existing TAA-Specific T Cells in the Circulation of NSCLC Patients
3.2. Pre-Existing TAA-Specific T Cells and Clinical Response
3.3. Immune Effectors in the Circulation of Pre-Existing Immunity Patients
3.4. Peripheral Blood Immune Suppressor Cells in PreI+ Patients
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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Stage IIIb (n = 35) | Stage III & IV (n = 17) | All Patients (n = 52) | ||
---|---|---|---|---|
Characteristics | Sub-Categories | Values | Values | Values |
Median age | 70 years (range 48–86 years) | 70 years (range 52–82 years) | 70 years (range 48–86 years) | |
Gender | Male | 28 (80%) | 12 (70.5%) | 40 (77%) |
Female | 7 (20%) | 5 (29.5%) | 12 (23%) | |
Stage | IIIb | 35 (100%) | 0 (0%) | 35 (67%) |
III (other than IIIb) | 0 (0%) | 10 (59%) | 10 (19%) | |
IV | 0 (0%) | 6 (35%) | 6 (12%) | |
Unknown | 0 (0%) | 1 (6%) | 1 (2%) | |
Location of primary tumor | Left lung | 12 (34%) | 4 (23.5%) | 16 (31%) |
Right lung | 22 (63%) | 10 (59%) | 32 (61.5%) | |
Both lungs | 1 (3%) | 0 (0%) | 1 (2%) | |
Unknown | 0 (0%) | 3 (17.5%) | 3 (5.5%) | |
Histological Type | Adenocarcinoma | 17 (49%) | 9 (53%) | 26 (50%) |
Squamous | 18 (51%) | 6 (35%) | 24 (46%) | |
Unknown | 0 (0%) | 2 (12%) | 2 (4%) | |
Smoking Status | Never | 4 (11.5%) | 0 (0%) | 4 (8%) |
Former | 20 (57%) | 3 (17.5%) | 23 (44%) | |
Curent | 11 (31.5%) | 10 (59%) | 21 (40%) | |
Unknown | 0 (0%) | 4 (23.5%) | 4 (8%) | |
<40 pack year | 4 (11%) | 5 (30%) | 9 (17%) | |
40–80 pack year | 13 (37%) | 2 (11.5%) | 15 (29%) | |
>80 pack year | 8 (23%) | 2 (11.5%) | 10 (19%) | |
Unknown | 10 (29%) | 8 (47%) | 18 (35%) |
PFS | OS | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
T-Cell Populations | ROC Cut Off | n | Median | 95% HR CI | p Value | Median | 95% HR CI | p Value | ||
% in CD3+CD8+ | PD1 | 25 | High | 40 | 268 | 0.437 to 2.173 | 0.949 | 411 | 0.445 to 3.100 | 0.744 |
Low | 12 | 296 | 390 | |||||||
% in CD3+CD8+ CD45RA+CD45RO- | Tnaive (RA+RO-CCR7+) | 55 | High | 17 | 397 | 0.250 to 1.477 | 0.271 | und | 0.303 to 2.575 | 0.821 |
Low | 35 | 258 | 411 | |||||||
Teff (RA+RO-CCR7−) | 40 | High | 36 | 268 | 0.273 to 2.295 | 0.668 | 450 | 0.150 to 1.718 | 0.276 | |
Low | 16 | 329 | 284 | |||||||
% in CD3+CD8+ CD45RA-CD45RO+ | Tcm (RA-RO+CCR7+) | 70 | High | 16 | 245 | 0.390 to 4.029 | 0.704 | und | 0.283 to 3.310 | 0.958 |
Low | 36 | 296 | 411 | |||||||
Tem (RA-RO+CCR7−) | 26 | High | 35 | 307 | 0.141 to 1.380 | 0.159 | 450 | 0.126 to 1.152 | 0.087 | |
Low | 17 | 258 | 284 | |||||||
% in CD3+CD4+ | PD1 | 2.2 | High | 35 | 321 | 0.202 to 1.187 | 0.114 | und | 0.093 to 0.712 | 0.0089 |
Low | 17 | 221 | 278 | |||||||
% in CD3+CD4+ CD45RA+CD45RO- | Tnaive (RA+RO-CCR7+) | 87 | High | 17 | 268 | 0.437 to 1.373 | 0.273 | 329 | 0.314 to 1.147 | 0.271 |
Low | 35 | 296 | 450 | |||||||
Teff (RA+RO-CCR7−) | 13 | High | 37 | 321 | 0.249 to 1.332 | 0.197 | und | 0.237 to 1.552 | 0.297 | |
Low | 15 | 268 | 329 | |||||||
% in CD3+CD4+ CD45RA-CD45RO+ | Tcm (RA-RO+CCR7+) | 55 | High | 27 | 221 | 0.485 to 2.214 | 0.926 | 411 | 0.328 to 1.943 | 0.620 |
Low | 25 | 307 | 390 | |||||||
Tem (RA-RO+CCR7−) | 40 | High | 26 | 296 | 0.463 to 2.127 | 0.984 | 450 | 0.509 to 3.00 | 0.637 | |
Low | 26 | 307 | 411 |
T Reg Cells | |||
---|---|---|---|
CD3CD4FOXP3 | PreI− | PreI+ | |
Mean | 8.39 | 7.76 | |
Std.Error | 1.106 | 1.163 | |
p-value | 0.678 | ||
CD25+CD127− | Mean | 5.55 | 5.91 |
Std.Error | 0.808 | 0.790 | |
p-value | 0.397 | ||
Basic Tregs CD25+CD127-FOXP3+ | Mean | 44.97 | 37.57 |
Std.Error | 3.622 | 4.392 | |
p-value | 0.118 | ||
CTLA4+ Tregs CD25+CD127-FOXP3+CTLA4+ | Mean | 22.55 | 16.29 |
Std.Error | 2.19 | 2.16 | |
p-value | 0.049 | ||
MDSCs | |||
CD14+CD15− M-MDSCs (%in CD33+CD11b+HLA-DR-Lin-) | PreI− | PreI+ | |
Mean | 3.38 | 3.18 | |
Std.Error | 0.34 | 0.39 | |
p-value | 0.713 | ||
CD14+CD15- iNOS+ M-MDSCs (%in CD33+CD11b+HLA-DR-Lin- CD14+CD15-) | Mean | 24.60 | 22.29 |
Std.Error | 3.085 | 3.038 | |
p-value | 0.551 | ||
CD14+CD15+ M-MDSCs (%in CD33+CD11b+HLA-DR-Lin-) | Mean | 1.069 | 1.327 |
Std.Error | 0.141 | 0.207 | |
p-value | 0.294 | ||
CD14+CD15+ iNOS+ M-MDSCs (%in CD33+CD11b+HLA-DR-Lin- CD14+CD15+) | Mean | 35.08 | 34.54 |
Std.Error | 2.59 | 3.59 | |
p-value | 0.653 |
Cell Populations | ROC Cut Off | n | Median | 95% HR CI | p Value | Median | 95% HR CI | p Value | |
---|---|---|---|---|---|---|---|---|---|
CD3CD4FOXP3 | 5 | High | 31 | 321 | 0.254 to 1.198 | 0.133 | 450 | 0.173 to 1.066 | 0.068 |
Low | 21 | 210 | 390 | ||||||
CD25+CD127- | 2.7 | High | 38 | 321 | 0.384 to 1.977 | 0.742 | und | 0.381 to 2.288 | 0.882 |
Low | 14 | 201 | 411 | ||||||
Basic Tregs | 43 | High | 18 | 268 | 0.572 to 2.625 | 0.600 | 411 | 0.392 to 2.209 | 0.871 |
Low | 34 | 296 | und | ||||||
CTLA4+ Tregs | 11 | High | 34 | 268 | 0.908 to 4.680 | 0.083 | 411 | 0.476 to 3.229 | 0.658 |
Low | 18 | und | und | ||||||
CD14+CD15- M-MDSCs | 2.3 | High | 35 | 268 | 0.444 to 2.18 | 0.967 | 411 | 0.387 to 2.404 | 0.938 |
Low | 17 | 296 | und | ||||||
CD14+CD15- iNOS+ M-MDSCs | 19 | High | 24 | 268 | 0.707 to 3.163 | 0.291 | 405 | 0.665 to 3.713 | 0.302 |
Low | 28 | 321 | und | ||||||
CD14+CD15+ M-MDSCs | 1.2 | High | 18 | 173 | 1.064 to 6.983 | 0.0047 | 321 | 1.118 to 7.617 | 0.0094 |
Low | 34 | 329 | und | ||||||
CD14+CD15+ iNOS+ M-MDSCs | 39 | High | 21 | 307 | 0.386 to 1.745 | 0.610 | und | 0.339 to 1.902 | 0.619 |
Low | 31 | 258 | 405 |
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Xagara, A.; Goulielmaki, M.; Fortis, S.P.; Kokkalis, A.; Chantzara, E.; Christodoulopoulos, G.; Samaras, I.; Saloustros, E.; Tsapakidis, K.; Papadopoulos, V.; et al. Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients. Cancers 2024, 16, 2393. https://doi.org/10.3390/cancers16132393
Xagara A, Goulielmaki M, Fortis SP, Kokkalis A, Chantzara E, Christodoulopoulos G, Samaras I, Saloustros E, Tsapakidis K, Papadopoulos V, et al. Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients. Cancers. 2024; 16(13):2393. https://doi.org/10.3390/cancers16132393
Chicago/Turabian StyleXagara, Anastasia, Maria Goulielmaki, Sotirios P. Fortis, Alexandros Kokkalis, Evangelia Chantzara, George Christodoulopoulos, Ioannis Samaras, Emmanouil Saloustros, Konstantinos Tsapakidis, Vasileios Papadopoulos, and et al. 2024. "Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients" Cancers 16, no. 13: 2393. https://doi.org/10.3390/cancers16132393