Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

Abstract

Several recent studies have shown that salvage chemotherapy following PD‐1 blockade produces high antitumor activity in some patients with non‐small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil‐to‐lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid‐derived suppressor cells and tumor‐associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time‐series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non‐responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non‐responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD‐1 blockade and chemotherapy.

Dynamic Biomarkers Indicate Immunological Benefits Provided by Ganoderma Spore Powder in Post-Operative Breast and Lung Cancer Patients: A Prospective Clinical Trial

“…In addition to the observed effect on lymphocyte immuno-phenotype, the active components of ganoderma spore powder inhibited the expression of iNOS and COX-2, as well as TNF-α and IL-6, through the suppression of LPS-based activation of NF-κB in RAW264.7 cells [32][33]. Similarly, we presented very interesting data on Th1/Th2 cell drift.…”

“…Lymphocyte counts indicate anti-tumor immunity [13]. A previous study con rmed that ganoderma spore powder inhibits the production of TNF-α and IL-6 preventing sustained immune response [32]. Against these data, surprisingly, we showed by multivariate analysis that low AGR was an independent poor prognostic factor related to PFS in the e cacy of ganoderma spore powder (HR = 1.572, p = 0.038).…”

Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

“…On the other hand, lymphocytes have been shown to be effective suppressors of cancer progression and to reflect host immunity [ 18 ]. And the NLR may be a more useful prognostic factor than the isolated leukocyte fraction as a marker reflecting both inflammation and the immune system function [ 4 , 17 , 18 , 19 , 20 , 21 ]. CRP and NLR have been studied as a prognostic biomarker of nivolumab in several cancers including NSCLC, metastatic renal cell carcinoma, metastatic melanoma, and R/M HNSCC [ 13 , 21 , 22 , 23 ].…”

“…For patients with progressive disease status after ICI treatment, another therapy sometimes could be administered to extend their life. Several studies have reported that salvage chemotherapy (SCT) administered after immunotherapy would be effective for patients with metastatic non-small-cell lung cancer (NSCLC), metastatic melanoma, B cell lymphoma, advanced gastric cancer, and metastatic urothelial carcinoma [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, SCT has been reported to be an effective treatment for HNSCC in R/M as well as other carcinomas and is attracting attention as a sequential treatment [ 10 , 11 ].…”

Novel strategies in immune checkpoint inhibitor drug development: How far are we from the paradigm shift?

“…Additional proposed markers of response include neutrophil‐to‐lymphocyte ratio (NLR), which has been reported to increase over time in non‐responders and decrease in responders, and inflammatory cytokines, which have also been correlated with response rates and toxicity 72–78 (Figure 3). Myeloid‐derived suppressor cell (MDSC) levels have been used to predict therapy response or resistance to ipilimumab treatment in metastatic melanoma patients, where increased frequency was associated with decreased efficacy, and vice versa 79,80 .…”