A comparison of the local immune status between the primary and metastatic tumor in colorectal cancer: a retrospective study

Abstract

BackgroundThe anticancer immune response has been reported to correlate with cancer progression. Tumor-infiltrating lymphocytes (TILs), which are one of the indicators of host immunity, affect the tumor growth, metastasis and chemoresistance. Both TILs in the primary tumor and those in the metastatic tumor have been reported to be a useful predictor of the survival and therapeutic outcome. However, the correlation between the density of TILs in the primary and metastatic tumor is unclear. The aim of this study was to elucidate the correlation between the density of TILs in the primary and metastatic tumor.MethodsA total of 24 patients with stage IV colorectal cancer who underwent concurrent resection of the primary tumor and liver metastasis were enrolled in order to assess the correlation between the density of TILs in the primary tumor and that in the metastatic tumor. Hematoxylin and eosin (HE)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by the measurement of the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. In addition, to evaluate TIL subsets and the activation/suppression status of the lymphocytes, immunohistochemistry for CD4, CD8, Forkhead boxprotein P3 (FOXP3), programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), inducible T-cell co-stimulator (ICOS), Glucocorticoid induced tumor necrosis factor receptor related protein (GITR), Human Leukocyte Antigen - antigen D Related (HLA-DR) and Granzyme B was performed, and the number of immunoreactive lymphocytes was counted.ResultsAccording to the evaluation using the HE-stained sections, the density of tumor-infiltrating mononuclear inflammatory cells in the primary tumor was significantly associated with that in the metastatic tumor. In addition, according to the immunohistochemistry evaluation, the density of CD4+, CD8+ and FOXP3+ TILs in the primary tumor and that in the metastatic tumor were significantly correlated with that in the metastatic tumor. Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B and the PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor.ConclusionsThe local immune status of the primary tumor was revealed to be similar to that of the metastatic tumor. This suggests that the evaluation of the local immunity of the primary tumor may be a substitute for the evaluation of the local immunity of the metastatic lesion. Therefore, information on the primary tumor may be useful when considering treatment strategies for metastatic lesions.

Study of Tumor Microenvironment and Host Response in Colorectal Cancer: Immunohistochemical and Clinicopathological Approach

“…For CD8+CTC is reported that CTCs are having an antitumor effect through its capability to prohibit target cells on being exposed to tumor cell antigen/human leukocyte antigen 1 complex for which their T cell receptors are specific, leading to the destruction of tumor cells by apoptosis and this improving prognosis. Our results were concordant with results reported by Deschoolmeester et al [36], Ling et al [19], Sideras et al [37], and Shibutani et al [38], regarding the antitumoral effect of CTC as it was significantly higher in early non-metastatic tumors.…”

Tumor-infiltrating IL-17A + cells determine favorable prognosis and adjuvant chemotherapeutic response in muscle-invasive bladder cancer

“…In addition, it is reported that the immune composition of metastatic site is close to that of the primary tumor. 35 Patients with a high frequency of intratumoral IL-17A+ cells might also have high infiltration of this cell population in their metastatic sites if the disease relapsed. It could be a possible reason for how these cells contribute to the therapeutic outcome but need to be confirmed in further study.…”

Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy

“…To the best of our knowledge, the local immune response impacts the clinical course not only from the primary tumour but also from metastatic liver lesions [18,19]. Thus, examining the effect of the tumour microenvironment on liver metastases might provide deeper insight into the appropriate immune biomarker ratio that may provide more accurate and reliable prognostic information for CLO.…”