PreprintReviewVersion 1Preserved in Portico This version is not peer-reviewed
The Role of Tumor Microenvironment in T Cell Redirecting Therapies of Large B Cell Lymphoma: Translating Lessons Learned from CAR-T to Bispecific Antibodies
Version 1
: Received: 12 September 2024 / Approved: 12 September 2024 / Online: 13 September 2024 (04:28:00 CEST)
How to cite:
Lepik, K. V.; Markelov, V. V. The Role of Tumor Microenvironment in T Cell Redirecting Therapies of Large B Cell Lymphoma: Translating Lessons Learned from CAR-T to Bispecific Antibodies. Preprints2024, 2024091052. https://doi.org/10.20944/preprints202409.1052.v1
Lepik, K. V.; Markelov, V. V. The Role of Tumor Microenvironment in T Cell Redirecting Therapies of Large B Cell Lymphoma: Translating Lessons Learned from CAR-T to Bispecific Antibodies. Preprints 2024, 2024091052. https://doi.org/10.20944/preprints202409.1052.v1
Lepik, K. V.; Markelov, V. V. The Role of Tumor Microenvironment in T Cell Redirecting Therapies of Large B Cell Lymphoma: Translating Lessons Learned from CAR-T to Bispecific Antibodies. Preprints2024, 2024091052. https://doi.org/10.20944/preprints202409.1052.v1
APA Style
Lepik, K. V., & Markelov, V. V. (2024). The Role of Tumor Microenvironment in T Cell Redirecting Therapies of Large B Cell Lymphoma: Translating Lessons Learned from CAR-T to Bispecific Antibodies. Preprints. https://doi.org/10.20944/preprints202409.1052.v1
Chicago/Turabian Style
Lepik, K. V. and Vladislav V. Markelov. 2024 "The Role of Tumor Microenvironment in T Cell Redirecting Therapies of Large B Cell Lymphoma: Translating Lessons Learned from CAR-T to Bispecific Antibodies" Preprints. https://doi.org/10.20944/preprints202409.1052.v1
Abstract
T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for optimization of their use with combination or consolidation strategies, which necessitates prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment.
While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in current knowledge and suggest that insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
