Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients.

Ana Margarida Barbosa,Henrique Pinto,Adhemar Longatto-Filho,Egídio Torrado,Juliana Campos,Rosete Nogueira,Sandra F. Martins,Olga Martinho,António G. Castro,Liliana Lobo

doi:10.3390/biology10080808

Abstract

Simple SummaryColorectal cancer (CRC) is amongst the deadliest cancers. Surgical excision of the primary tumor is the curative intent treatment; however, recurrence occurs in approximately 20% of patients. Therefore, novel staging protocols are crucial to inform clinicians which patients will recur. In this study, we explored the prognostic potential of tumor-infiltrating lymphocytes. Our data did not reveal any association between intratumor lymphocyte infiltrations with clinical or pathological data. On the other hand, the presence of CD3+, CD8+, or FoxP3+ lymphocyte infiltration in the tumor invasive margins were associated with markers of good prognosis. Despite this, we were not able to find any statistically significant alterations in the overall survival of patients, even though high infiltrations of FoxP3+ T lymphocytes in the tumor margin resulted in an increased overall survival of 14 months. Taken together, our data show that the location and type of tumor-infiltrating lymphocytes are associated with the pathogenesis of CRC; however, only high FoxP3+ T lymphocyte infiltrations are inclined to indicate favorable prognosis.Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3+, CD8+, and FoxP3+ T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3+, CD8+, or FoxP3+ T lymphocytes were associated with TNM stages I-II (p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases (p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3+ T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3+, CD8+, or FoxP3+T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3+ T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.

Highlights

Colorectal cancer (CRC) is the third most common type of cancer worldwide, and its occurrence is responsible for nearly 10% of all deaths related to malignancies [1]
colorectal cancer (CRC) prognosis, we determined the infiltration of CD3+, CD8+, or FoxP3+ T lymphocytes within the tumor, tumor margins, and in the normal adjacent tissue by immunohistochemistry
When we compared the proportion of infiltrating lymphocytes that were CD8+ or FoxP3+, we found a high intratumor infiltration of CD8+ T lymphocytes in 52% (97/187) and a high intratumor infiltration of FoxP3+ T lymphocytes in 53% (103/196) of samples (Table 2)

Summary

Introduction

Colorectal cancer (CRC) is the third most common type of cancer worldwide, and its occurrence is responsible for nearly 10% of all deaths related to malignancies [1]. The incidence of CRC has been low at ages younger than 50 years; in recent years, there has been a rising incidence of CRC at these ages [2]. The cornerstone of curative intent treatment for CRC remains surgical excision of the primary tumor [4]. While this approach is curative for most patients, recurrence of CRC disease occurs in approximately 20% of patients [5]. After tumor resection, clinicians often have follow-up appointments with patients to detect any recurrence at an early and treatable stage These follow-ups have unraveled the need for novel predictive prognosis biomarkers and well-established staging protocols to inform clinicians which patients will recur

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