M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study

Abstract

IntroductionThe efficacy and safety of immunotherapy have been widely recognized in gastrointestinal-related cancers. However, the efficacy of neoadjuvant camrelizumab for locally advanced esophageal squamous cell carcinoma (ESCC) has not been firmly established. This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response.MethodsWe enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy.ResultsA total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15).ConclusionsNeoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

“…The role of macrophage in ltration in the prediction of response to neoadjuvant treatment in ESCC has been identi ed. 11 Elevated tumor-associated macrophages (TAM) density in ESCC is correlated with tumor progression and shorter survival. Our previous study showed that nCRT markedly induced the in ltration of M2 macrophage.…”

“…6 More M1 macrophages predicted well response to neoadjuvant camrelizumab combined with chemotherapy. 11 Pre-existing T cells in tumor contributed to the well response to neoadjuvant anti-PD-L1 immunotherapy in ESCC. 6 A CCR4/CCR6 chemokine-based model was considered useful to predict the bene ts from neoadjuvant chemoradiotherapy combined with ICB therapy.…”

A computed tomography-based nomogram for neoadjuvant chemotherapy plus immunotherapy response prediction in patients with advanced esophageal squamous cell carcinoma

“…Due to the absence of the phenomenon of pseudoprogression in this study, tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as follows ( 23 ): complete response (CR) was the disappearance of all target lesions; partial response (PR) was at minimum a 30% reduction in the sum of the longest target lesion diameters using the sum of the longest target lesion diameters at baseline as reference; progressive disease (PD) was at minimum a 20% increase in the sum of the longest target lesion diameters using the minimum sum of the longest target lesion diameters recorded since the start of treatment (rock bottom) as reference, or the appearance of at least one new lesion; and stable disease (SD) was neither PR nor PD. The patients with CR or PR according to RECIST (v.1.1) within two treatment cycles were considered “responders,” while those who suffered from PD or SD were considered “non-responders.” As reported ( 24 ), the application of iRECIST had no impact on response-related endpoints, compared to RECIST 1.1, and we used RECIST 1.1 to assess the tumoral treatment response.…”