Sir,
We are most grateful to Professor Park, McMillan and Roxburgh for their interest and valuable comments on our manuscript titled ‘Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis’ (Mei et al, 2014). They cited several recently published studies with consistent results, pointing out some other important relationships among inflammatory cell infiltrate, the tumour microenvironment and immune response in colorectal cancer (CRC), which were not discussed in detail in our original publication because of the length of the publication. Therefore, some major concerns, such as the following, must be addressed.
First, the analytical methods used in our publication for the generalised tumour inflammatory infiltrate were relatively standardised ones and included the Jass classification, the Klintrup—Makinen (K–M) criteria and Crohn’s-like reaction criteria. The pooled hazard ratios and 95% CIs for overall survival, cancer-specific survival and disease/recurrence-free survival in a subset of highly generalised tumour inflammatory infiltrate were <1, indicating a robust survival marker for CRC. However, conflicting results (with HRs and 95% CI across 1) were noted among individual studies as heterogeneity originated from local inflammatory reaction grading systems, patient characteristics, follow-up schemes and some other factors, which was especially evident among individual T-cell subtypes. More detailed stratifications by tumour location, stage, grade and other microenvironmental components should be proposed.
Second, there have been conflicting reports regarding the relationship between inflammatory cell infiltrate and local inflammatory response for CRC prognosis, justifying the need for further analyses. In our meta-analysis, we did not include some of the mentioned studies because of the following reasons.
-
1)
absence of time-to-event (survival) data for high-grade over low-grade immune cell inflammation (Klintrup et al, 2005);
-
2)
sharing of the same cohort (Richards et al, 2012a, 2012b);
-
3)
investigating the outcome of tumour inflammatory cell infiltrate in primary operable invasive ductal breast cancer (Mohammed et al, 2012);
-
4)
study publication after the deadline of August 2013 (Vayrynen et al, 2013; Richards et al, 2014).
To minimise variation between studies, currently, standardised and robust methods for assessment of the generalised inflammatory cell infiltrate used in clinical practice are urgently needed. Forrest et al (2014) developed an automated, computer-aided scoring method that proved to be more facilitated, objective, accurate, reproducible and cost-effective than the manual method. We assumed that some larger prospective studies could be proposed to validate the robustness of association between not only the generalised inflammatory cell infiltrate but also the subsets of T lymphocytes as well and CRC survival.
References
Forrest R, Guthrie GJ, Orange C, Horgan PG, McMillan DC, Roxburgh CS (2014) Comparison of visual and automated assessment of tumour inflammatory infiltrates in patients with colorectal cancer. Eur J Cancer 50 (3): 544–552.
Klintrup K, Mäkinen JM, Kauppila S, Väre PO, Melkko J, Tuominen H, Tuppurainen K, Mäkelä J, Karttunen TJ, Mäkinen MJ (2005) Inflammation and prognosis in colorectal cancer. Eur J Cancer 41 (17): 2645–2654.
Mei Z, Liu Y, Liu C, Cui A, Liang Z, Wang G, Peng H, Cui L, Li C (2014) Tumour-infiltrating inflammation and prognosis in co lorectal cancer: systematic review and meta-analysis. Br J Cancer 110: 1595–1605.
Mohammed ZM, Going JJ, Edwards J, Elsberger B, Doughty JC, McMillan DC (2012) The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer. Br J Cancer 107 (5): 864–873.
Richards CH, Flegg KM, Roxburgh CS, Going JJ, Mohammed Z, Horgan PG, McMillan DC (2012a) The relationships between cellular components of the peritumoural inflammatory response, clinicopathological characteristics and survival in patients with primary operable colorectal cancer. Br J Cancer 106 (12): 2010–2015.
Richards CH, Roxburgh CSD, Anderson JH, McKee RF, Foulis AK, Horgan PG, McMillan DC (2012b) Prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer. Br J Surg 99 (2): 287–294.
Richards CH, Roxburgh CS, Powell AG, Foulis AK, Horgan PG, McMillan DC (2014) The clinical utility of the local infl ammatory response in colorectal cancer. Eur J Cancer 50 (2): 309–319.
Vayrynen JP, Tuomisto A, Klintrup K, Makela J, Karttunen TJ, Makinen MJ (2013) Detailed analysis of inflammatory cell infiltration in colorectal cancer. Br J Cancer 109 (7): 1839–1847.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Mei, Z., Liu, Y., Liu, C. et al. Response to comment on ‘Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis’. Br J Cancer 111, 2372–2373 (2014). https://doi.org/10.1038/bjc.2014.285
Published:
Issue Date:
DOI: https://doi.org/10.1038/bjc.2014.285