Tumor-Infiltrating Lymphocytes Demonstrate Distinct Behavior in the Tumoral and Peritumoral Microenvironment After Neoadjuvant Chemotherapy in Patients with Resected Adenocarcinoma of the Gastric or Gastroesophageal Junction: Results from a Single Center
by
, , ,
Fotios Seretis
1,*
,
Antonia Panagaki
2,
Sofia Ritsatou
3,
Eleni Stoupi
3,
Andreas Theodorou
1,
Spyridon Smparounis
1,
Chrysoula Glava
3,
Maria Theochari
4 and
Tania Triantafyllou
1,* 1
First Propaedeutic Department of Surgery, Hippokrateion General Hospital of Athens, National and Kapodistrian University of Athens, 11527 Athens, Greece
2
Department of Gastroenterology, “Konstantopouleio-Patision” General Hospital of Nea Ionia, 14233 Athens, Greece
3
Department of Pathology, Hippokrateion General Hospital of Athens, 11527 Athens, Greece
4
Department of Medical Oncology, Hippokrateion General Hospital of Athens, 11527 Athens, Greece
*
Authors to whom correspondence should be addressed.
Cancers 2025, 17(12), 1971; https://doi.org/10.3390/cancers17121971
Submission received: 17 March 2025
/
Revised: 7 June 2025
/
Accepted: 10 June 2025
/
Published: 13 June 2025
(This article belongs to the Section Methods and Technologies Development)
Simple Summary
Adenocarcinomas of the esophagogastric and gastric areas represent complex entities. Their management currently entails an increasing use of neoadjuvant therapies (mainly chemotherapy in Europe) followed by radical surgery. The effect that neoadjuvant treatments inflict on the anti-tumoral response of the host’s immune system remains largely unknown. We hereby report results from a single center on tumor-infiltrating lymphocytes assessed on surgical resection specimens after curative intent surgery in patients with adenocarcinomas of the stomach or esophagogastric junction areas. Our results suggest that tumor-infiltrating lymphocytes do not correlate with the tumor regression in the primary tumor but do correlate with the regression of the disease in the affected lymph nodes.
Abstract
Background/Objectives: Adenocarcinomas of the esophagogastric and gastric areas are often managed with a multimodal treatment including neoadjuvant chemotherapy and surgery. The impact of neoadjuvant chemotherapy on the host’s antitumoral immune response remains largely unknown. Methods: A retrospective review of a single-institution cohort of patients with adenocarcinoma of the stomach or esophagogastric area undergoing curative intent surgery after neoadjuvant chemotherapy FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) was reviewed. After institutional ethics approval, pathologic slides were re-reviewed and tumor-infiltrating lymphocyte scores were calculated. Tumor-infiltrating lymphocytes (TILs) were studied in conjunction with tumor regression scores (TRG) and the degree of regression in the involved lymph nodes as well as in correlation with the lymph node ratio (the ratio of involved lymph nodes over the total number of lymph nodes resected). Results: A total of 106 patients were reviewed. No statistical correlation could be established between the tumor-infiltrating lymphocyte scores and the degree of regression in the primary tumor as well as with the partial response to chemotherapy of pathologically involved lymph nodes. The TIL score also did not correlate with the lymph node ratio in our patient cohort. A strong correlation was noted between TILs and lymph nodes that completely regressed after neoadjuvant chemotherapy. Conclusions: Tumor-infiltrating lymphocytes do not correlate with the response of the primary tumor or the partial response of the involved lymph nodes, but only with the complete response to neoadjuvant chemotherapy of tumor-involved lymph nodes. Our study focuses on the effects of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes compared to the effects on the primary tumor and the involved lymph nodes.
