We read with interest the recent review article by Brummel et al. [1] on the prognostic significance of tumour-infiltrating lymphocytes (TILs) across various cancer types. We congratulate the authors for this timely review of the topic, and we would like to emphasise the emerging, important role of TILs in tumour characterisation, which was not highlighted in their review. Incorporation of TILs as a modifier to supplement the commonly used tumour-node-metastasis (TNM) classification, designated as TNM-Immune staging system, has been proposed recently [2]. It is widely accepted that different cancers with the same TNM stage may present with extreme variations in their pre-existing adaptive immunity [3]. Thus, incorporating a parameter which assesses immune response in the TNM system seems clinically relevant in predicting tumour behaviour. Such a proposal allows incorporation of the immune response in cancer classification and even in clinical therapeutical decision making.
The prognostic significance of the TNM-Immune staging system has been introduced previously in some studies [4–6] including our recent study on oropharyngeal cancer published in British Journal of Cancer [6]. In our multicentre study on early-stage oral tongue cancer [5], the TNM-Immune staging system based on incorporation of an overall score of TILs, showed a prognostic value superior to that of the routine TNM classification (American Joint Committee on Cancer eighth edition, AJCC 8). In breast cancer, emerging evidence indicates that TILs can up- or downgrade prognosis related to the stage of the AJCC 8, so that stage I patients with low TILs may have a worse survival than stage II patients with high TILs. This has been recently reported by de Jong et al. [7] who found that stage II cases with high infiltration of stromal TILs were associated with a better survival than stage IB cases presenting with low infiltration of TILs. In colon cancer, findings from a large series of cases strongly supported implementation of the immunoscore (densities of CD3 and CD8 positive cells) into the TNM-Immune staging system [8]. In lung cancer, TNM-Immune staging has shown a promising prognostic value [9]. In addition, immunoscore based on the analysis of subsets of TILs added a significant prognostic impact to the TNM staging of lung cancer [4].
In the daily practice, incorporation of the immunoscore into the TNM staging can be an important step towards individualised prognostication and treatment planning. The strategy of incorporating a clinically relevant prognostic marker to the AJCC 8 as a modifier refining the TNM staging has been considered for some cancers [10]. With respect to the prognostic significance of TILs, it is advised to remember that clinical decision making based on the use of a single prognosticator only is not recommended. Therefore, a promising approach is to use TILs as a part of the staging system, i.e. to refine the TNM staging. Further validation of the above results on the TNM-Immune staging is desirable towards its establishment in clinical practice.
Author contributions
The three authors wrote, revised, and approved the final version of the manuscript.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
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