Tumor microenvironment features decipher the outperformance of neoadjuvant immunochemotherapy over chemotherapy in resectable non-small cell lung cancer

Abstract

This study evaluated the efficacy of neoadjuvant immunochemotherapy (Io+Chemo) versus chemotherapy alone (Chemo) in resectable non–small cell lung cancer (NSCLC) in a real-world setting. The association of tumor immune microenvironment (TIME) with pathologic response to different neoadjuvant therapies was also explored.Stage I−III NSCLC patients who received Io+Chemo or Chemo alone followed by surgery were included in the study. Tumor tissues collected during surgery were subjected to TIME evaluation using multiplex immunohistochemistry to measure immune cell subsets, including T cells, B cells, NK cells, and macrophages. Fifty-five patients were included, including 24 treated with neoadjuvant Io+Chemo and 31 with Chemo alone. Io+Chemo induced significantly higher major pathologic response (MPR) (75.0% vs. 38.7%, P = 0.0133) and numerically better pathologic complete response (pCR) (33.3% vs. 12.9%, P = 0.1013) than Chemo. Compared with tumors with Chemo, tumors with Io+Chemo demonstrated a significantly higher ratio of M1 macrophage density in the tumor to that in the stroma (P = 0.0446), more abundant CD8+ cells in the stroma (P = 0.0335), and fewer PD-L1+CD68+ cells in both tumor and stroma. pCR/MPR patients displayed significantly higher density of CD3+, CD3+CD4+, CD20+, CD56 bright cell subsets and more tertiary lymphoid structures and significantly lower density of PD-L1+CD68+ and CD3+CD4+Foxp3+cells in the tumor or stroma. This study favored neoadjuvant Io+Chemo over Chemo and revealed the TIME features underlying the outperformance of Io+Chemo over Chemo.

Tumor immune microenvironment remodeling and prognosis of patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy with and without immunotherapy

“…In addition, neoadjuvant PD-1/L1 inhibitors could utilize high tumor antigen levels in the primary tumor to enhance T-cell priming [23]. Other studies have shown that neoadjuvant immunochemotherapy can upregulate the expression of PD-L1 and TILs [24]. Both neoadjuvant immunochemotherapy and neoadjuvant radiotherapy can upregulate PD-L1 expression [25], which supports our current research ndings.…”

The efficacy of neoadjuvant immunotherapy combined with chemotherapy in resectable stage II–IV non-small cell lung cancer: a preliminary study

“…Moreover, for 26 patients in whom lymph node metastasis was highly suspected, there was no tumor cell residue in lymph nodes as confirmed pathologically after neoadjuvant therapy. Previous research ( 7 ) indicates that neoadjuvant immunochemotherapy can eradicate tumor cells by impacting the tumor microenvironment. The concomitant use of immunotherapy with chemotherapy could stimulate the immune system, enhancing the efficacy of the body’s T and B cells in eliminating tumor cells for an extended period.…”

Complete pathological remission and tertiary lymphoid structures are associated with the efficacy of resectable NSCLC receiving neoadjuvant chemoimmunotherapy: A double-center retrospective study

“… 17 The presence of TLS has also provided new insights into the mechanism by which neoadjuvant chemoimmunotherapy is preferable to chemotherapy from the perspective of the tumor microenvironment. 18 However, few studies have explored the exact relationship between TLS and clinical prognosis in terms of its expression and maturation.…”