Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer
Abstract
:Simple Summary
Abstract
1. The Importance of Immune Surveillance in HER2-Positive Breast Cancer
2. Tumor-Infiltrating Lymphocytes in HER2-Positive Breast Cancer
3. Clinical Relevance of Different Phenotypes of Immune Infiltrates
3.1. CD4+ and CD8+ T Cells
3.2. Treg Cells
3.3. B Cells
3.4. NK Cells
3.5. Tumor-Associated Macrophages
4. Immunotherapy in HER2-Positive Breast Cancer
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Trial | Reference (Clinical Trial) | Setting | Number of Patients | Treatment Arms | Parameters | Results | p-Value | Reference (TILs Evaluation) |
---|---|---|---|---|---|---|---|---|
GeparSixto | [32] | Neoadjuvant | 580 | Paclitaxel/ doxorubicin/trastuzumab Paclitaxel/ doxorubicin/trastuzumab/carboplatin | Association between TILs (as a continuous parameter) or LPBC (>60%) and pCR rates | 10% increase in TILs was significantly associated with pCR. sTILs and LPBC were independent predictor factors for pCR. LPBC tumors treated with PMCb showed high-response pCR rates. | 0.001 0.001; 0.001 0.006 | [30] |
FinHER | [33] | Early | 232 | Docetaxel/ FEC Docetaxel/ FEC/ Trastuzumab | Association between TILs (as a continuous variable) and trastuzumab benefit | 10% increase in TILs was significantly associated with reduction in DDFS. | 0.025 | [34] |
APHINITY | [35] | Early | 4804 | Chemotherapy/ trastuzumab Chemotherapy/ trastuzumab/ pertuzumab | Association between TILs (as a continuous variable) and 6-year IDFS after addition of Pertuzumab | TILs percentage appeared to be more predictive of pertuzumab treatment effect than clinical composite risk score. | n.s. | [36] |
N9831 | [37] | Early | 945 | Doxorubicin/ cyclophosphamide/ paclitaxel (Arm A) Doxorubicin/ cyclophosphamide/ paclitaxel/ trastuzumab (Arm C) | Association between sTILs (>60%) and RFS after addition of trastuzumab | Patients with high and low sTILs did not show differences in 10-year RFS. | 0.63 | [38] |
NRG/NSABP B-31 | [37] | Early | 1581 | Chemotherapy Chemotherapy/ Trastuzumab | Association of sTILs (as a semi-continuous variable) and trastuzumab benefit in DFS | Increase in sTILs was significantly associated with improved DFS. There was not association between sTILs and trastuzumab benefit. | 0.001 0.65 | [39] |
NeoALTTO | [40] | Early | 387 | Chemotherapy/ trastuzumab Chemotherapy/ lapatinib Chemotherapy/ trastuzumab/ lapatinib | Associations among presence of TILs (>5%), pCR, and EFS | Levels of TILs greater than 5% were associated with higher pCR rates. Every 1% increase in TILs was associated with a decrease in EFS. | 0.01 0.002 | [41] |
ShortHER | [42] | Early | 866 | Anthracycline/ taxane/ trastuzumab 1 year (Arm A) Anthracycline/ taxane/ trastuzumab 9 weeks (Arm B) | Association between TILs (as a semicontinuous and binary variable) with DDFS | 10% increase in TILs was an independent prognostic factor for DDFS. 10% increase in TILs was a significant prognostic factor in arm B Arm A patients with <20% TILs showed better DDFS compared with arm B patients. | 0.002 0.009; 0.021 | [43] |
CLEOPATRA | [44] | Advanced | 678 | Docetaxel/ trastuzumab Docetaxel/ trastuzumab/ pertuzumab | Association between sTILs (as a semicontinuous variable) and PFS, OS and pertuzumab benefit | There was not significant association between TILs and PFS. 10% increase in sTILs was significantly associated with better OS. There were not significant differences by sTILs for PFS or OS after pertuzumab addition. | 0.063 0.0014 0.23; 0.21 | [45] |
MA.31 | [46] | Advanced | 427 | Taxane/ trastuzumab Taxane/lapatinib | Association between TILs (>5%) and PFS after addition of lapatinib | Low CD8+ cytotoxic sTILs were associated with worse PFS in patients treated with lapatinib. | 0.03 | [47] |
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Luque, M.; Sanz-Álvarez, M.; Morales-Gallego, M.; Madoz-Gúrpide, J.; Zazo, S.; Domínguez, C.; Cazorla, A.; Izarzugaza, Y.; Arranz, J.L.; Cristóbal, I.; et al. Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer. Cancers 2022, 14, 6034. https://doi.org/10.3390/cancers14246034
Luque M, Sanz-Álvarez M, Morales-Gallego M, Madoz-Gúrpide J, Zazo S, Domínguez C, Cazorla A, Izarzugaza Y, Arranz JL, Cristóbal I, et al. Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer. Cancers. 2022; 14(24):6034. https://doi.org/10.3390/cancers14246034
Chicago/Turabian StyleLuque, Melani, Marta Sanz-Álvarez, Miriam Morales-Gallego, Juan Madoz-Gúrpide, Sandra Zazo, Carolina Domínguez, Alicia Cazorla, Yann Izarzugaza, Juan Luis Arranz, Ion Cristóbal, and et al. 2022. "Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer" Cancers 14, no. 24: 6034. https://doi.org/10.3390/cancers14246034
APA StyleLuque, M., Sanz-Álvarez, M., Morales-Gallego, M., Madoz-Gúrpide, J., Zazo, S., Domínguez, C., Cazorla, A., Izarzugaza, Y., Arranz, J. L., Cristóbal, I., & Rojo, F. (2022). Tumor-Infiltrating Lymphocytes and Immune Response in HER2-Positive Breast Cancer. Cancers, 14(24), 6034. https://doi.org/10.3390/cancers14246034