Neoadjuvant immunotherapy for resectable esophageal cancer: A review

Qing Li, Ting Liu, Zhenyu Ding, Qing Li, Ting Liu, Zhenyu Ding

Abstract

Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, the 5-year survival rate of EC is still dismal. For patients with resectable disease, neoadjuvant chemoradiotherapy (nCRT) in combination with esophagectomy is the mainstay of treatment. However, the pathological complete response (pCR) rate to nCRT of 29.2% to 43.2% is not satisfactory, and approximately half of the patients will develop either a locoregional recurrence or distant metastasis. It is, therefore, necessary to explore novel and effective treatment strategies to improve the clinical efficacy of treatment. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has significantly changed the treatment paradigm for a wide variety of advanced cancers, including EC. More recently, increasing clinical evidence has demonstrated that neoadjuvant immunotherapy can potentially improve the survival of patients with resectable cancers. Furthermore, accumulating findings support the idea that chemotherapy and/or radiotherapy can activate the immune system through a variety of mechanisms, so a combination of chemotherapy and/or radiotherapy with immunotherapy can have a synergistic antitumor effect. Therefore, it is reasonable to evaluate the role of neoadjuvant immunotherapy for patients with surgically resectable EC. In this review, we discuss the rationale for neoadjuvant immunotherapy in patients with EC, summarize the current results of utilizing this strategy, review the planned and ongoing studies, and highlight the challenges and future research needs.

Keywords: chemotherapy; esophageal cancer (EC); immune checkpoint inhibitor (ICI); immunotherapy; neoadjuvant therapy; radiotherapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Li, Liu and Ding.

Figures

Figure 1
Figure 1
Potential mechanism of neoadjuvant immunotherapy. (A) This figure provides a stepwise overview of the potential mechanism of the antitumor effect of ICIs in the presence of a primary tumor. (B) After surgical removal of the primary tumor, T cells in the blood circulation can continue to exert antitumor effects to clear any remaining tumor cells. (C) After surgical removal of the primary tumor, immune memory cells prevent any postoperative recurrence and metastasis. PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1; MHC, major histocompatibility complex; TCR, T-cell receptor; TME, tumor microenvironment; DCs, dendritic cells.
Figure 2
Figure 2
This figure provides a stepwise overview of the potential mechanism of the synergistic antitumor effect of immune checkpoint inhibitors (ICIs) combined with radiotherapy and/or chemotherapy. PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1; MHC, major histocompatibility complex; TCR, T-cell receptor; TME, tumor microenvironment; DCs, dendritic cells.
Figure 3
Figure 3
Published clinical studies on immune checkpoint inhibitor (ICI) neoadjuvant therapy in resectable esophageal cancer (EC). (A) The radiologic response. (B) The pathological response. (C) The safety results. ICIs, immune checkpoint inhibitors; CRT, chemoradiotherapy; ORR, objective response rate; DCR, disease control rate; pCR, pathologic complete response; MPR, major pathological response; AEs, adverse events; ESCC, esophageal squamous cell carcinoma; EAC, esophageal adenocarcinoma; NA, not available.
Figure 4
Figure 4
Challenges of neoadjuvant immunotherapy for esophageal cancer. ICIs, immune checkpoint inhibitors; CRT, chemoradiotherapy, AEs, adverse events; EC, esophageal cancer.

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