Tumour burden and efficacy of immune-checkpoint inhibitors

Dall’Olio, Filippo Gustavo; Marabelle, Aurélien; Caramella, Caroline; Garcia, Camilo; Aldea, Mihaela; Chaput, Nathalie; Robert, Caroline; Besse, Benjamin

doi:10.1038/s41571-021-00564-3

Cited by 166 publications

(126 citation statements)

References 162 publications

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“… 17 In addition to immunosuppressive effects, conventional chemotherapeutics have immunostimulatory effects, which can be beneficial in the context of immunotherapy. 18–20 The effectiveness of chemotherapy was also shown to be dependent upon the preexisting intratumoral T-cells, and Immunoscore. 8 , 9 , 21 …”

Section: The Consensus Immunoscorementioning

confidence: 99%

“…Genomic alteration of malignant cells, favoring the emergence of immunogenic tumor neoantigens, has been associated with differential T-cell responses and to sensitivity to immunotherapy. 18 , 20 , 22 Tumor immunogenicity and immune cells involved in anti-tumor responses may also be affected by epigenomic alterations. 23 In addition, DNA damage response (DDR) deficiency has also emerged as an important determinant of tumor immunogenicity.…”

Section: The Consensus Immunoscorementioning

confidence: 99%

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Immune sunrise: from the immunome to the cancer immune landscape

2022

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The complex dynamics of the tumor-immune interaction during tumor progression have been characterized by integrating genomic and proteomic experiments. The Immunome, a reference compendium of markers for the majority of immune cell subpopulations was used to describe the immune landscape in cancer. The immune contexture is at the cornerstone in the success of cancer immunotherapies. Markers with the highest clinical relevance were summarized as the consensus immunoscore. This immune evaluation refines the prognosis of the patients and the chemotherapy decision-making process and was introduced as essential and desirable diagnostic criteria into three major international guidelines.

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Section: The Consensus Immunoscorementioning

confidence: 99%

Section: The Consensus Immunoscorementioning

confidence: 99%

Immune sunrise: from the immunome to the cancer immune landscape

2022

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“…A possible explanation for the interaction of our new high/low-risk classification with irT effect on survival may be related to tumor burden. Several studies indicated that tumor burden and number of metastatic sites are negative predictive factors for immunotherapy efficacy [ 26 , 27 , 28 ]. It is suggested that the immune penetrance is lower when the tumor burden is high and that advanced tumors’ microenvironments have greater populations of immune suppressive cells [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies indicated that tumor burden and number of metastatic sites are negative predictive factors for immunotherapy efficacy [ 26 , 27 , 28 ]. It is suggested that the immune penetrance is lower when the tumor burden is high and that advanced tumors’ microenvironments have greater populations of immune suppressive cells [ 26 , 27 ]. Thus, in the high-risk group with a high tumor burden and lower chance of immune activation, the subgroup that was able to effectively activate their immune system (as seen by the surrogate marker of irT) had improved survival prospects.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Sagie

Gadot

Levartovsky

et al. 2022

Cancers

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Immune checkpoint inhibitors (CPI) are indicated for metastatic renal cell carcinoma (mRCC). Immune-related thyroiditis (irT), an immune-related adverse event (irAE), affects up to 30% of patients. We aimed to determine whether irT is associated with overall survival in mRCC. A retrospective cohort study of 123 consecutive patients treated with CPI for mRCC in a single center between 2015 and 2020 was conducted. Disease risk stratification was assessed by two methods: Heng criteria and a novel dichotomic stratification system to “Low risk” versus “High risk” adding number of metastatic sites. Thirty-eight percent of patients developed irT. In the general cohort, irT was not associated with a survival benefit. However, irT was associated with better survival in the poor risk group per Heng criteria (n = 17, HR = 0.25, p = 0.04) and in the novel “High risk” group (HR = 0.28, n = 42, p = 0.01), including after accounting for covariates in multivariate analysis (HR = 0.27, p = 0.003). Having any irAE was associated with improved survival in the whole cohort, with no significant correlation of any specific irAE, in either the whole cohort or the “High risk” group. We conclude that irT is an early and prevalent irAE, associated with prolonged survival in patients with poor/“High” risk mRCC.

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“…As already recognized by Rudolph Virchow in the nineteenth century (2,3), the critical role of inflammatory processes in atherogenesis and carcinogenesis is now well-established and has prompted investigation of strategies to combat these deadly diseases by modulating underlying immune responses (4)(5)(6)(7)(8)(9)(10). Several anti-cancer immunotherapies, such as cytokines, antibodies targeting immune cell receptors, or immune checkpoints, dendritic cell therapy, and chimeric antigen receptor (CAR) T cell therapy, already found their way into clinical practice and thereby revolutionized cancer treatment (9,11). In stark contrast, clinically approved immunotherapies for CVD are still not available [except for antibodies targeting proprotein convertase subtilisin/kexin 9 (PCSK9) to lower low-density lipoprotein (LDL) cholesterol, representing an immunotherapeutic approach in a broader sense (12,13)].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapeutic Strategies in Cancer and Atherosclerosis—Two Sides of the Same Coin

Nettersheim

Picard

Hoyer

et al. 2022

Front. Cardiovasc. Med.

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The development and clinical approval of immunotherapies has revolutionized cancer therapy. Although the role of adaptive immunity in atherogenesis is now well-established and several immunomodulatory strategies have proven beneficial in preclinical studies, anti-atherosclerotic immunotherapies available for clinical application are not available. Considering that adaptive immune responses are critically involved in both carcinogenesis and atherogenesis, immunotherapeutic approaches for the treatment of cancer and atherosclerosis may exert undesirable but also desirable side effects on the other condition, respectively. For example, the high antineoplastic efficacy of immune checkpoint inhibitors, which enhance effector immune responses against tumor cells by blocking co-inhibitory molecules, was recently shown to be constrained by substantial proatherogenic properties. In this review, we outline the specific role of immune responses in the development of cancer and atherosclerosis. Furthermore, we delineate how current cancer immunotherapies affect atherogenesis and discuss whether anti-atherosclerotic immunotherapies may similarly have an impact on carcinogenesis.

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Tumour burden and efficacy of immune-checkpoint inhibitors

Cited by 166 publications

References 162 publications

Immune sunrise: from the immunome to the cancer immune landscape

Immune sunrise: from the immunome to the cancer immune landscape

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Immunotherapeutic Strategies in Cancer and Atherosclerosis—Two Sides of the Same Coin

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