Table 3.
The association between TILs and pathologic response in neoadjuvant studies
| Reference | Study | Manner of sample collection | Regimen | Assay | Marker | Type of TILs | Sample size | Definition of pCR | Correlation with pCR |
|---|---|---|---|---|---|---|---|---|---|
| Hornychova et al. (2008) [41] | Single institute | Retrospective | Anthracycline-taxane-based regimens | IHC | CD3 | iTIL | 73 | ypT0/Tis | CD3+iTIL (p = .004, univariate) |
| ypN0 | |||||||||
| Denkert et al. (2010) [42] | GeparDuo | Prospective | EC-Doc (GeparDuo) | H&E | TILs | sTIL | 1,058 | ypT0/Tis | sTILs (continuous, per 10% increase) (p = .001, multivariate) |
| GeparTrio | TAC±vinorBlbine/capecitabine (GeparTrio) | iTIL | ypN0 | LPBC (binary ≥ 60%) (p = .001, multivariate) | |||||
| Denkert et al. (2015) [51] | Geparsixto | Prospective | Anthracycline-taxane plus carbioplatin vs Anthracycline-taxane | H&E | TILs | sTIL | 580 | ypT0/Tis | sTILs (continuous, per 10% increase) (p = .001, multivariate) |
| mRNA assay | 12 Immune mRNA markers | iTIL | 481 | ypN0 | 12 Immune mRNA markers were predictive for increased pCR | ||||
| West et al. (2011) [44] | Public gene expression data from EORTC 10994/BIG00-01 | Prospective | FEC vs TET | Gene expression data | Gene expression data | Not associated | 99 | Undefined | High TIL signature correlate with pCR (p = .001, multivariate) |
| Ono et al. (2012) [52] | Single institute | Retrospective | Anthracycline-based; cyclophosphamide-based or taxane-based regimens | H&E | TILs | sTIL | 92 TNBC | ypT0 | Total TILs correlate with pCR (p = .015, multivariate) |
| iTIL | |||||||||
| Yamaguchi et al. (2012) [53] | Single institute | Retrospective | Anthracycline-taxane-based regimens | H&E | TILs | Total TILs | 68 | ypT0/Tis | Total TILs correlate with pCR (p<.001, multivariate) |
| Oda et al. (2012) [54] | Institutional | Retrospective | Paclitaxel followed by FEC | IHC | CD8, FOXP3, IL17F | iTIL | 180 | ypT0ypN0 | FOXP3 positively correlated with pCR (p = .014, multivariate) |
| Schmidt et al. (2012) [35] | Public gene expression data (7 cohorts) | Retrospective | Anthracycline-based regimen | Gene expression data | Gene expression data | Not associated | 845 | Undefined | IGKC positively correlated with pCR (p<.001) |
| Issa-Nummer et al. (2013) [55] | GeparQuinto Predict study | EC-D | EC followed by D | H&E | TILs | sTIL | 313 HER2– | ypT0ypN0 | sTILs and LPBC associated with pCR (p = .01, multivariate) |
| iTIL | LPBC associated with pCR (p = .003, multivariate) | ||||||||
| Seo et al. (2013) [25] | Single institute | Retrospective | Anthracycline-taxane-based regimens | IHC | CD8, CD4, FOXP3 | iTILs | 153 | ypT0ypN0 | CD8 positively correlated with pCR (p = .003, multivariate) |
| Lee et al. (2013) [56] | Single institute | Retrospective | Anthracycline-taxane-based regimens | H&E | TILs, CD3, CD8, FOXP3 | sTILs | 175 | ypT0ypN0 | sTIL positively correlated with pCR (p = .024, multivariate) |
| IHC | |||||||||
| Nabholtz et al. (2014) [57] | Phase II TVA study | Prospective | FEC with/without D with panitumumab | IHC | CD8 | Not associated | 47 | ypT0/Tis | CD8 positively correlated with pCR (p = .000003, univariate) |
| ypN0 |
CD8 positively correlated with pCR (p = .000003, univariate).
TIL, tumor-infiltrating lymphocyte; pCR, pathological complete response; IHC, immunohistochemistry; iTIL, intratumoral tumor-infiltrating lymphocyte; H&E, hematoxylin and eosin; sTIL, stromal tumor-infiltrating lymphocyte; LPBC, lymphocyte predominant breast cancer; FEC, 5-fluorouracil, epirubicin, cyclophosphamide; TET, docetaxel, epirubin and docetaxel; TNBC, triple-negative breast cancer; IL, interleukin; IGKC, gene encoding for immunoglobulin kappa constant; D, docetaxel; HER2, human epidermal growth factor receptor 2; FOXP3, forkhead box P3 protein.