Predictive biomarkers for response to immune checkpoint inhibition

Shum, Benjamin; Larkin, James; Turajlic, Samra

doi:10.1016/j.semcancer.2021.03.036

Cited by 86 publications

(89 citation statements)

References 180 publications

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“…Thus, predicting response remains challenging and PD-L1 expression alone was insufficient which restrain the application of ICI to some extent. Several potentially predictive biomarkers also have been studied which can be classified as tumorrelated markers, tumor microenvironment-related biomarkers and host-related biomarkers (54)(55)(56). Tumor-related markers mainly including tumor mutational burden (TMB), microsatellite instability (MSI) and mismatch repair deficiency (MMR).…”

Section: Discussionmentioning

confidence: 99%

Unexpected Favorable Outcome to PD-1 Antibody Plus Lenvatinib in a Patient With Recurrent Intestinal Follicular Dendritic Cell Sarcoma: A Case Report and Literature Review

2021

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BackgroundFollicular dendritic cell sarcoma (FDCS) is an uncommon malignant cancer, and there is no standard treatment to date. Resection followed by adjuvant chemotherapy or radiation is considered the most commonly used strategy for treatment. However, the treatment for patients who have progressed after systemic treatment is more controversial.Case summaryIn this case report, we describe a 57-year-old man with primary small intestine FDCS where surgery and second-line systemic chemotherapy failed. After disease progression (PD), the patient received sintilimab plus lenvatinib as third-line treatment and achieved a progression-free survival (PFS) with 7 months.ConclusionThis is the first report of a FDCS patient treated with immune checkpoint inhibitors (ICIs) and antiangiogenic agents, sintilimab and lenvatinib, as third-line therapy. Our case provides a potential therapeutic option for patients with FDCS who progressed after multiline therapy.

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Section: Discussionmentioning

confidence: 99%

Unexpected Favorable Outcome to PD-1 Antibody Plus Lenvatinib in a Patient With Recurrent Intestinal Follicular Dendritic Cell Sarcoma: A Case Report and Literature Review

2021

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“…The efficacy of immunotherapy varies greatly across patients and cancer types, and biomarkers that can identify the tumors that would be most responsive to specific immunotherapies are an area of active investigation (74). Candidate biomarkers of efficacy including PD-L1 expression, mutational burden, neoantigens, tumor infiltrating lymphocytes, and radiographic characteristics are under active study (75)(76)(77)(78)(79).…”

Section: Biomarkers Of Efficacy and Toxicitymentioning

confidence: 99%

Immunotherapy Combined With Radiation Therapy for Genitourinary Malignancies

Ukleja

Kusaka²,

Miyamoto³

2021

Front. Oncol.

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Immunotherapy drugs have recently been approved by the Food and Drug Administration for the treatment of several genitourinary malignancies, including bladder cancer, renal cancer, and prostate cancer. Preclinical data and early clinical trial results suggest that immune checkpoint inhibitors can act synergistically with radiation therapy to enhance tumor cell killing at local irradiated sites and in some cases at distant sites through an abscopal effect. Because radiation therapy is commonly used in the treatment of genitourinary malignancies, there is great interest in testing the combination of immunotherapy with radiation therapy in these cancers to further improve treatment efficacy. In this review, we discuss the current evidence and biological rationale for combining immunotherapy with radiation therapy, as well as emerging data from ongoing and planned clinical trials testing the efficacy and tolerability of this combination in the treatment of genitourinary malignancies. We also outline outstanding questions regarding sequencing, dose fractionation, and biomarkers that remain to be addressed for the optimal delivery of this promising treatment approach.

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“…Current predictive biomarkers of response to ICB efficacy include tumor mutational burden (TMB), neoantigen load, PD-L1 expression, Microsatellite Instability (MSI) status, and diversity of immune cells in the TME. 3 High TMB with neoantigen load has been reported as an independent predictor of favorable outcome across various cancer types and there are well-defined factors (both cell intrinsic and extrinsic) contributing to TMB generation. 3 MSI-High tumors arise due to germline variations, as well as epigenetic repression of mismatch repair genes, and MSI is currently tested as a marker for several immunotherapy trials.…”

Section: Introductionmentioning

confidence: 99%

“… 3 High TMB with neoantigen load has been reported as an independent predictor of favorable outcome across various cancer types and there are well-defined factors (both cell intrinsic and extrinsic) contributing to TMB generation. 3 MSI-High tumors arise due to germline variations, as well as epigenetic repression of mismatch repair genes, and MSI is currently tested as a marker for several immunotherapy trials. 3 The most well-established biomarker, PD-L1, has been beneficial in guiding patient selection for immune checkpoint blockade.…”

Section: Introductionmentioning

confidence: 99%

“… 3 MSI-High tumors arise due to germline variations, as well as epigenetic repression of mismatch repair genes, and MSI is currently tested as a marker for several immunotherapy trials. 3 The most well-established biomarker, PD-L1, has been beneficial in guiding patient selection for immune checkpoint blockade. The regulation of PD-L1 in tumors is quite complex and other immune checkpoints contribute to negative immune regulation.…”

Section: Introductionmentioning

confidence: 99%

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