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Fig 1.

Prisma study flow diagram.

The search strategy performed in this article led to the initial selection of 623 potential papers. After duplicates were removed, a total of 449 papers were identified. From these, 317 articles were excluded based on title and abstract. Further investigation of the remaining 132 full text articles led to the exclusion of 100 articles and the inclusion of 32 studies for the qualitative synthesis, with nine of them included in the meta-analysis.

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Fig 2.

Waffle plot: Each box represents an article which measured a type of cell (A) or a marker (B).

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Fig 3.

Risk of bias summary.

Review authors’ judgments about each risk of bias item for each included study. a) The study question and/or objective of the study is clear. b) Eligibility/selection criteria for the study population are specified and described in advance. c) Study participants were representative of the test/service/intervention in the general or clinical population of interest. d) Eligible participants who met the pre-specified entry criteria were enrolled. e) The sample size was sufficiently large to provide confidence in the findings. f) The test/service/intervention was clearly described and uniformly administered across the study population. g) Outcome measures were pre-specified, clearly defined, valid, reliable, and consistently assessed across all study participants. h) Individuals assessing outcomes were blinded to participants’ exposures/interventions i) Loss to follow-up after baseline was 20% or less and loss to follow-up was accounted for in the analysis. j) Statistical methods for changes in outcomes from pre to post intervention were examined. Statistical tests were performed that provided p values for pre- to post-intervention changes. k) Whether an ethics committee approved the protocol, or whether patients signed an informed consent form is clearly described. l) The antibodies, clones and brand used in the labeling were described (For the technique that applies). m) Results were clearly presented.

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Table 1.

Distribution of the number of articles (n) according to the trend (low, no difference, high) for each of the analyzed cell.

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Fig 4.

TILs meta-analysis.

Influence of NAC in the TILs density of BC tumors. Forest plot for the different outcomes regarding TILs density before and after NAC. The forest plot displays the SMD (squares) and 95% confidence interval of the individual studies. The diamond in each plot indicates the overall estimate and 95% confidence interval.

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Fig 5.

CD3+ T cells meta-analysis.

Influence of NAC in the CD3+ T cells infiltration of BC tumors. Forest plot for the different outcomes regarding CD3+ T cells infiltration before and after NAC. The forest plot displays the SMD (squares) and 95% confidence interval of the individual studies. The diamond in each plot indicates the overall estimate and 95% confidence interval.

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Fig 6.

CD4+ T cells meta-analysis.

Influence of NAC in the CD4+ T cells infiltration of BC tumors. Forest plot for the different outcomes regarding CD4+ T cells infiltration before and after NAC. The forest plot displays the SMD (squares) and 95% confidence interval of the individual studies. The diamond in each plot indicates the overall estimate and 95% confidence interval.

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Fig 7.

CD8+ T cells count meta-analysis.

Influence of NAC in the CD8+ T cells count of BC tumors. Forest plot for the different outcomes regarding CD8+ T cells count before and after NAC. The forest plot displays the SMD (squares) and 95% confidence interval of the individual studies. The diamond in each plot indicates the overall estimate and 95% confidence interval.

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Fig 8.

CD8+ T cells infiltration meta-analysis.

Influence of NAC in the CD8+ T cells infiltration of BC tumors. Forest plot for the different outcomes regarding CD8+ T cells infiltration before and after NAC. The forest plot displays the SMD (squares) and 95% confidence interval of the individual studies. The diamond in each plot indicates the overall estimate and 95% confidence interval.

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Fig 9.

FoxP3+ Tregs infiltration meta-analysis.

Influence of NAC in the FoxP3+ Tregs infiltration of BC tumors. Forest plot for the different outcomes regarding FoxP3+ Tregs infiltration before and after NAC. The forest plot displays the SMD (squares) and 95% confidence interval of the individual studies. The diamond in each plot indicates the overall estimate and 95% confidence interval.

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Table 2.

Distribution of the number of articles (n) according to the trend (low, no difference, high) for each of the analyzed immune checkpoint.

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Table 3.

Distribution of the number of articles (n) according to the trend (low, no difference, high) for each of the analyzed cytokines.

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