A novel immune monitoring platform for patients with gastrointestinal cancer.

Authors

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Mojun Zhu

Mayo Clinic, Rochester, MN;

Mojun Zhu , Wen Wee Ma , Harry H. Yoon , Joleen M. Hubbard , Robert R. McWilliams , Haidong Dong

Organizations

Mayo Clinic, Rochester, MN;

Research Funding

Conquer Cancer Foundation of the American Society of Clinical Oncology
Conquer Cancer Foundation of the American Society of Clinical Oncology

Background: Understanding the impact of anticancer therapies on immune system is critical to successful design and incorporation of immunotherapies. We developed a novel immune monitoring platform that measures the relative amount of circulating effector T cells and antitumor cytotoxicity of circulating immune cells. We previously showed that this assay can differentiate patients’ clinical response to anti-PD-1 therapy. Here, we applied this assay to patients with gastric or gastroesophageal junction adenocarcinoma (GGEA) who received chemoradiation or chemotherapy-based therapies. Methods: Patients underwent peripheral blood collection at baseline and during follow-up. Levels of circulating effector T cells (CX3CR1+NKG7+/CD3+CD8+) were quantified by flow cytometry using peripheral blood mononuclear cells (PBMCs). Antitumor cytotoxicity of circulating immune cells was evaluated by co-culturing CD3/CD28 activated PBMCs with calcein-AM labeled GGEA tumor cells (FLO-1). Antitumor cytotoxicity of individual patients’ PBMCs was calculated based on the amount of calcein released by dead tumor cells. Results: In a pilot study of 8 patients with mismatch repair-proficient (pMMR) GGEA, the changes in the frequency of effector T cells appeared to be associated with radiographic response to treatment based on RECIST (3 partial response [PR], 3 stable disease [SD], and 2 progressive disease [PD]). The median interval between sequential blood collections was 64 days and an increase in effector T cells was observed in patients with PD. Antitumor cytotoxicity was evaluated in 4 patients who did not receive targeted therapies or immune checkpoint inhibitors. Two of these patients (a, b) had blood collected at the time of diagnosis (treatment naïve) and after neoadjuvant therapy. One developed pulmonary metastases after chemoradiation while the other had significant tumor shrinkage after chemotherapy. The decrease in antitumor cytotoxicity of PBMCs was less in the patient with PD (-19.4%) than the one with PR (-48.5%). Two patients (c, d) had blood collected twice while receiving the same chemotherapy for metastatic disease (not treatment naïve). The decrease in antitumor cytotoxicity of PBMCs was less in the patient with SD (-0.3%) than the one with PR (-14.5%). Conclusions: We demonstrated the feasibility of using PBMCs to monitor immune response to anticancer therapies. Our data raise the possibility that the amount of circulating effector T cells and antitumor cytotoxicity of PBMCs may be associated with tumor burden in patients with pMMR solid tumors.

Treatment response by RECISTCX3CR1+NKG7+/CD3+CD8+ (%)
BaselineFollow-upChanges
Partial response31.116.6↓↓
Partial responsea30.819.5
Partial responsec17.68.15
Stable diseased23.120.8
Stable disease12.15.5
Stable disease5.245.83
Progressive diseaseb20.331.4
Progressive disease12.719.6

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Abstract Details

Meeting

2023 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Cancers of the Esophagus and Stomach and Other GI Cancers

Track

Esophageal and Gastric Cancer,Other GI Cancer

Sub Track

Translational Research

Citation

J Clin Oncol 41, 2023 (suppl 4; abstr 424)

DOI

10.1200/JCO.2023.41.4_suppl.424

Abstract #

424

Poster Bd #

J8

Abstract Disclosures

Funded by Conquer Cancer