Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer

Abstract

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

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.…”

Tumor-infiltrating Lymphocytes Predict the Chemotherapeutic Outcomes in Patients with Stage IV Colorectal Cancer

“…those with high-TILs, have a better prognosis than those with a weaker reaction. Furthermore, the density of TILs has been reported to correlate with the efficacy of chemotherapy and radiotherapy (9,10,24). Although some problems remain, such as the unification of methods for the evaluation and elucidation of the functions for each subset, TILs are now receiving a great deal of attention as potential new biomarkers.…”

“…Tumor-infiltrating lymphocytes (TILs), which reflect the immune status of the host (7), have been reported to correlate with the clinical outcome, including the chemotherapeutic outcome in patients with various types of cancer (8)(9)(10). However, the method of measuring TILs has differed among previous reports (11)(12)(13)(14)(15).…”

The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer

“…Although it is unclear whether or not immune cell infiltration in small biopsies reflected those in surgically resected specimens, tumor-infiltrating lymphocytes from small biopsy specimens have been shown to predict therapy responses in advanced NSCLC. 38 Another limitation of this study was that these findings were not confirmed in a validation cohort. More importantly, although immune cell infiltrates were quantitatively similar, we did not evaluate functionality of infiltrating immune cells, as this can only be evaluated prospectively from fresh tissue.…”