Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes-Reference-Cited by-同舟云学术

Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes

Published:2024-04-17 Issue:7 Volume:12 Page:814-821
ISSN:2326-6066
Container-title:Cancer Immunology Research
language:en
Short-container-title:

Author:

König David¹²³^ORCID,Sandholzer Michael T.¹^ORCID,Uzun Sarp⁴^ORCID,Zingg Andreas¹^ORCID,Ritschard Reto¹²³^ORCID,Thut Helen¹³^ORCID,Glatz Katharina⁴^ORCID,Kappos Elisabeth A.⁵^ORCID,Schaefer Dirk J.⁵^ORCID,Kettelhack Christoph⁶^ORCID,Passweg Jakob R.³⁷^ORCID,Holbro Andreas³⁷⁸^ORCID,Baur Katharina³⁷^ORCID,Medinger Michael⁷^ORCID,Buser Andreas³⁷⁸^ORCID,Lardinois Didier⁹^ORCID,Jeker Lukas T.¹³¹⁰^ORCID,Khanna Nina¹³¹¹^ORCID,Stenner Frank²^ORCID,Kasenda Benjamin²³^ORCID,Homicsko Krisztian¹²¹³¹⁴^ORCID,Matter Matthias⁴^ORCID,Rodrigues Mantuano Natalia¹^ORCID,Zippelius Alfred¹²³^ORCID,Läubli Heinz¹²³^ORCID

Affiliation:

1. Department of Biomedicine, University of Basel, Basel, Switzerland. 1

2. Division of Medical Oncology, University Hospital Basel, Basel, Switzerland. 2

3. Innovation Focus Cell Therapies, University Hospital Basel, Basel, Switzerland. 3

4. Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland. 4

5. Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, Switzerland. 5

6. Visceral Surgery, Clarunis University Center for Gastrointestinal and Liver Disease, University Hospital and Claraspital Basel, Basel, Switzerland. 6

7. Division of Hematology, University Hospital Basel, Basel, Switzerland. 7

8. Blood Donation Center Basel, Basel, Switzerland. 8

9. Department of Thoracic Surgery, University Hospital Basel, Basel, Switzerland. 9

10. Division of Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland. 10

11. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. 11

12. AGORA Cancer Research Center, Lausanne, Switzerland. 12

13. Ludwig Institute for Cancer Research, Lausanne, Switzerland. 13

14. Department of Oncology, CHUV, Lausanne, Switzerland. 14

Abstract

Abstract Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients with melanoma, although long-term responses seem restricted in patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of secondary resistance to TIL-ACT possibly due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To the best our knowledge, this is the first case of clonal selection of a pre-existing nondominant tumor cell clone; this report demonstrates the mechanism involved in secondary resistance to TIL-ACT that can potentially change current clinical practice because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before treatment with TIL-ACT.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Publisher

American Association for Cancer Research (AACR)

Link

https://aacrjournals.org/cancerimmunolres/article-pdf/doi/10.1158/2326-6066.CIR-23-0757/3443025/cir-23-0757.pdf

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