Prognostic Effect of Epithelial and Stromal Lymphocyte Infiltration in Non–Small Cell Lung Cancer

Abstract

Purpose: The major value of prognostic markers in potentially curable non-small cell lung cancer (NSCLC) should be to guide therapy after surgical resection. In this regard, the patients' immune status at the time of resection may be important and also measurable. The immune system has paradoxical roles during cancer development. However, the prognostic significance of tumorinfiltrating lymphocytes is controversial.The aim of this study is to elucidate the prognostic significance of epithelial and stromal lymphocyte infiltration in NSCLC. Experimental Design: Tissue microarrays from 335 resected NSCLC, stage I to IIIA were constructed from duplicate cores of viable and representative neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the epithelial and stromal CD4 No such relation was noted for epithelial CD4 + cells. Furthermore, a low level of stromal CD8 + lymphocyte infiltration was associated with an increased incidence of angiolymphatic invasion (P = 0.032). In multivariate analyses, a high number of stromal CD8 + (P = 0.043) and CD4 + (P = 0.002) cells were independent positive prognostic factors for disease-specific survival.Conclusions: High densities of CD4 + and CD8 + lymphocytes in the stroma are independent positive prognostic indicators for resected NSCLC patients. This may suggest that these cells are mediating a strong antitumor immune response in NSCLC.

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

“…Several groups demonstrated that increased CD8 + tumor-infiltrating lymphocytes and even PD-1 + tumor-infiltrating lymphocytes were a favorable prognostic factor in various types of cancers. [45][46][47][48] These studies suggested that increased PD-1 + tumor-infiltrating lymphocytes may reflect a subset of immune cells previously activated by the antitumor immune response, and thereby correlated with a favorable clinical outcome. 48 However, PD-1 + T cells have been regarded as functionally exhausted rather than activated because of chronic and persistent antigenic exposure from either viral infection or the tumor microenvironment, suggesting that the PD-1 + /CD8 + tumor-infiltrating lymphocyte ratio might reflect attenuated cytotoxicity of CD8 + T cells against tumors.…”

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

“…39 Also, in NSCLC CD4 C TILs have been described as a positive prognostic factor. [41][42][43] Their influence on patients' prognosis can be explained by the important role of CD4 C TILs in antitumor immunity. Via secretion of several immunoregulatory cytokines, such as IFNg and interleukin-2, they provide help for stimulating CD8 C TILs and natural killer cells.…”

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

“…34 However, when considering the primary localization of infiltrating cells, high COX-2 expression was associated significantly with the presence of intratumoral FOXP3-positive Tregs but not with the intratumoral presence of CD4-positive T cells, suggesting mechanisms within the tumor microenvironment of UM that favor the recruitment and/or preferential enrichment of Tregs over conventional, CD4-positive T cells. 10 The role of T-cell infiltration for the clinical course of malignant diseases is controversial, and various studies have linked it to a better 5 or worse 6 prognosis, depending on the type of cancer. These results emphasize the complexity of the immunologic host antitumor response and the regulatory factors involved.…”