Dataset Information

Immunotherapy resistance in solid tumors: mechanisms and potential solutions.

ABSTRACT: While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural immunity and immunotherapies through primary (innate) and secondary (acquired) mechanisms of resistance, and it considers available and emerging therapeutic approaches to overcoming immunotherapy resistance.

SUBMITTER: Lefler DS

PROVIDER: S-EPMC10896138 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immunotherapy resistance in solid tumors: mechanisms and potential solutions.

Lefler Daniel S DS Manobianco Steven A SA Bashir Babar B

Cancer biology & therapy 20240222 1

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patie ...[more]

PMID: 38389121

Similar Datasets

Project description:Immunotherapy has revolutionized the treatment of both hematological malignancies and solid tumors. The use of immunotherapy has improved outcome for patients with cancer across multiple tumor types, including lung, melanoma, ovarian, genitourinary, and more recently breast cancer with durable responses seen even in patients with widespread metastatic disease. Despite the promising results, immunotherapy still helps only a subset of patients due to overall low response rates. Moreover, the response to immunotherapy is highly cancer specific and results have not been as promising in cancers that are considered less immunogenic. The strategies to improve immunotherapy responses have focused on biomarker selection, like PD-L1 status, and usage of combinatorial agents, such as chemotherapy, targeted therapy, and radiotherapy. Of particular interest, DNA-damaging agents have the potential to enhance the response to immunotherapy by promoting neoantigen release, increasing tumor mutational burden, and enhancing PD-L1 expression. Poly-ADP-ribose polymerase (PARP) inhibitors are one such class of drugs that has shown synergy with immunotherapy in preclinical and early clinical studies. PARP-based therapies work through the inhibition of single-strand DNA repair leading to DNA damage, increased tumor mutational burden, making the tumor a more attractive target for immunotherapy. Of the solid tumors reviewed, breast, ovarian, and prostate cancers have demonstrated efficacy in the combination of PARP inhibition and immunotherapy, predominately in BRCA-mutated tumors. However, initial investigations into wildtype BRCA and gastrointestinal tumors have shown moderate overall response or disease control rates, dependent on the tumor type. In contrast, although a number of clinical trials underway, there is a paucity of published results for the use of the combination in lung or urothelial cancers. Overall this article focuses on the promise of combinatorial PARP inhibition and immunotherapy to improve patient outcomes in solid tumors, summarizing both early results and looking toward ongoing trials.

Dataset Information

Immunotherapy resistance in solid tumors: mechanisms and potential solutions.

Publications

Immunotherapy resistance in solid tumors: mechanisms and potential solutions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets