Table 1 Clinical details of the included studies
Author, year of publication | Country | Type of TNBC | No. of participants | TIL detection method | Location of TILs | Definition of high TIL level | TIL phenotype | Chemotherapy | Median follow-up (m) | Short-term prognosis | Target long-term prognosis |
|---|---|---|---|---|---|---|---|---|---|---|---|
Adams et al. 2014 [18] | USA | Operable TNBC | 481 | HE | Intra-epithelial and stromal | TILs involving 50% of either tumor stroma or cell nests | None specified | AT&AC | 127 | not specified | DFS OS |
AiErken et al. 2017 [19] | China | TNBC | 215 | HIC | Total and stromal | TILs-low (range, 0 to 10%); TILs-moderate (range, 11 to 40%); TILs-Marked (range, 41 to 100%). | PD-L1 | Anthracyclines or Anthracyclines + Taxino | 67.7 | not specified | DFS OS |
Althobiti et al. 2018 [20] | USA | TNBC | 230 | HE | Average stromal | Quantity of TILs was evaluated as percentage of TILs present in the stroma | CD3+ CD8+ FOXP3+ CD20+ CD68+ | Not specified | not specified | not specified | OS |
Asano et al. 2018 [21] | Japan | TNBC | 61 | HE | Stromal | > 10% was considered positive for TILs | None specified | Neoadjuvant | 40.8 | pCR | DFS |
Byun et al. 2018 [22] | South Korea | TNBC | 109 | IHC | not specified | TILs were divided into (≥33% vs. < 33%) PD-L1 expression was categorized into two groups according to the final scores: low expression (< 100) and high expression (≥100). | PD-L1+ TILs | Not specified | 76 | not specified | DFS OS |
Cerbelli et al. 2017 [23] | Italy | TNBC received standard NACT | 54 | IHC and HE | Stromal | TILs were quantified as a percentage of the stromal area of the tumor and expressed as a continuous parameter. | PD-L1 | 4 cycles of doxorubicin + cyclophosphamide Q3W followed by 12 cycles of paclitaxel weekly | not specified | pCR | not specified |
Denkert et al. 2015 [24] | Germany | TNBC | 255 | IHC and HE | Stromal | TILs involving 60% of either tumor stroma or cell nests | PD1 PDL1 CD8+ FOXP3 | Not specified | not specified | pCR | not specified |
Denkert et al. 2018 [25] | Germany | TNBC | 906 | HE | Stromal | Three predefined categories: low TILs (0–10%), intermediate TILs (11–59%), or high TILs (60–100%). | None specified | (4 cycles of doxorubicin + cyclophosphamide Q3W followed by 12 cycles of paclitaxel weekly) | for OS, 62.8 months; median follow-up for DFS, 63.3 months | pCR | DFS OS |
Dieci et al. 2014 [26] | France | TNBC patients with residual disease | 293 | HE | Intratumoral and stromal | High-TIL if It-TIL and/or Str-TIL > 60% | None specified | Neoadjuvant chemotherapy | 75.6 | not specified | OS |
Dieci et al. 2015 [27] | France | TNBC | 199 | HE | Intratumoral and stromal | Cases were defined as High-TIL if It-TIL and/or Str-TIL > 60% | None specified | Not specified | 152.4 | not specified | OS |
Galvez et al. 2018 [28] | Peru | TNBC | 100 | HE | Stromal | Cases were defined as High-TIL if Str-TIL > 50% | None specified | Neoadjuvant chemotherapy | not specified | pCR | not specified |
Goto et al. 2018 [29] | Japan | TNBC treated with neoadjuvant chemotherapy | 39 | HE and IHC | Stromal | High if TILs occupied > 10% of the stromal area | CD8+ FOXP3+ | standardised NAC protocol consisting of four courses of FEC100 (500 mg/m2 fluorouracil, 100 mg/m2 epirubicin and 500 mg/m2 cyclophosphamide) every 3 weeks, followed by 12 courses of 80 mg/m2 paclitaxel administered weekly. | not specified | not specified | OS |
Herrero-Vicent et al. 2017 [30] | Spain | TNBC treated with neoadjuvant chemotherapy | 164 | HE | None specified | not specified | not specified | Standardised NAC protocol | not specified | pCR | not specified |
Hida et al. 2016 [31] | Japan | TNBC | 381 | HE | None specified | Classified as high if TILs score > 50% | not specified | Neoadjuvant chemotherapy | 45 | pCR | not specified |
Jang et al. 2018 [32] | South Korea | TNBC | 231 | HE | Stromal | Classified TILS as high (> 10%) | not specified | Anthracycline-based chemotherapy | 117 | not specified | DFS OS |
Kim et al. 2017 [33] | South Korea | TNBC | 40 | HE | Stromal | Classified TILS score as high (> 60%). | Glutaminase+ TILs | An adjuvant methotrexate-based regimen | 78.3 | not specified | DFS |
Krishnamurti et al. 2017 [34] | USA | TNBC without neoadjuvant treatments | 157 | HE | Stromal | TILs estimated in intervals as < 5, 5–10%, 11–50%, and > 50% | not specified | Not specified | not specified | not specified | DFS OS |
Lee et al. 2016 [35] | South Korea | TNBC | 769 | HE | Stromal | TILs defined as the mean percentage of stroma of invasive carcinoma infiltrated by lymphocytes and plasma cells in 10% increments | not specified | Four cycles of adjuvant anthracycline and cyclophosphamide | not specified | not specified | DFS OS |
Leon-Ferre et al. 2018 [36] | USA | TNBC | 605 | HE | Stromal and intratumoral | Lymphocyte-predominant breast cancer (LPBC) was defined as having > 50% stromal or intratumoral TILs | Not specified | Anthracycline and taxane | 124.8 | not specified | DFS OS |
Li et al. 2016 [37] | USA | TNBC | 136 | IHC and HE | not specified | TILs were evaluated as the percentage of intratumoral stroma covered by mononuclear lymphocytes. | PD-L1 PD-1 | Not specified | 49.03 | not specified | DFS OS |
Loi et al. 2014 [38] | Australia | newly diagnosed TNBC | 145 | HE | Stromal | TILs ≥50% | not specified | Not specified | 62 | not specified | OS |
Luen et al. 2019 [39] | France | TNBC treated with neoadjuvant chemotherapy | 375 | HE and IHC | Stromal | Quantification of TILs in the tumor stroma was recorded as a percentage of occupied stromal areas. | not specified | Anthracycline and taxane; Anthracycline alone; and Taxane alone | 72 | not specified | OS |
Matsumoto et al. 2016 [40] | Singapore | Primary TNBC | 232 | HE and IHC | Stromal and intratumoral | Median TIL value as the cut-off for high vs. low | CD4+ CD8+ | Not specified | not specified | not specified | DFS OS |
McIntire et al. 2018 [41] | USA | TNBC | 76 | HE and IHC | None specified | TILs within the entire tumor were estimated at 5% intervals | CD8+ | Not specified | 110 | not specified | DFS OS |
Miyashita et al. 2014 [42] | Japan | TNBC | 110 | IHC | Stromal and intratumoral | None specified | CD8+ FOXP3+ | Not specified | not specified | pCR | not specified |
Mori et al. 2017 [43] | Japan | TNBC | 248 | IHC | Stromal and intratumoral | PD-L1+ was defined as expression in ≥5% of TILs | PD-L1 | None specified | 68 | not specified | OS |
O’Loughlin et al. 2018 [44] | Ireland | TNBC | 75 | HE | stromal | LPBC was defined as having > 50% stromal TILs | None specified | None specified | not specified | pCR | not specified |
Ono et al. 2012 [45] | Japan | TNBC received NAC and subsequent surgical therapy | 102 | IHC | None specified | TIL score classified as high if the sum was 3–5 | None specified | neoadjuvant anthracycline-based regimens | not specified | pCR | not specified |
Park et al. 2016 [46] | South Korea | Early TNBC | 133 | HE | Stromal and intratumoral | Classified TILS as high (> 10%) | not specified | None specified | None specified | not specified | DFS OS |
Pruneri et al. 2016 [47] | USA | TNBC | 724 | Multiplexed QIF staining | Stromal | LPBC defined as > 50% stromal TILs | not specified | Anthracycline + Taxanes ± CMF Anthracycline ± CMF | 82.8 | not specified | DFS OS |
Pruneri et al. 2016 [48] | Switzerland | TNBC | 897 | HE | Stromal | None specified | not specified | CMF CMF + AC | 98.4 | not specified | DFS OS |
Ruan et al. 2018 [49] | China | TNBC treated with neoadjuvant chemotherapy | 166 | None specified | Stromal and intratumoral | Classified TILS as high (> 10%) | not specified | Anthracycline + paclitaxel Paclitaxel + platinum | not specified | pCR | not specified |
Seo et al. 2013 [7] | South Korea | TNBC | 38 | IHC | None specified | Median values of TILs used as cut off, and infiltration of TILs categorized as low or high. | CD4+ CD8+ FOXP3+ | AC, AD; and ACT | not specified | pCR | not specified |
Tian et al. 2016 [50] | China | Primary invasive TNBCs | 425 | HE | Stromal and intratumoral | LPBC was categorized as tumors involving ≥50% lymphocytic infiltration in either tumor stroma or cell nests | not specified | Anthracyclines; Anthracyclines + Taxanes | 48 | not specified | DFS OS |
Urru et al. 2018 [51] | Italy | TNBC | 841 | IHC | Stromal | None specified | not specified | Not specified | 51.6 | not specified | DFS OS |
West et al. 2013 [52] | Canada | TNBC | 82 | IHC | Stromal | None specified | FOXP3+ TILs | Not specified | not specified | not specified | DFS |
Yeong et al. 2017 [53] | Singapore | TNBC | 164 | IHC | None specified | Cut-off median percentages used were also compatible to the accepted clinical pathological practices | FOXP3+ | Not specified | not specified | not specified | DFS OS |