Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab

Riaz, Nadeem; Havel, Jonathan J.; Makarov, Vladimir; Desrichard, Alexis; Urba, Walter J.; Sims, Jennifer S.; Hodi, F. Stephen; Martín‐Algarra, Salvador; Mandal, Rajarsi; Sharfman, William H.; Bhatia, Shailender; Hwu, Wen Jen; Gajewski, Thomas F.; Slingluff, Craig L.; Chowell, Diego; Kendall, Sviatoslav M.; Han, Chang; Shah, Rachna; Kuo, Fengshen; Morris, Luc G.T.; Sidhom, John-William; Schneck, Jonathan P.; Horak, Christine E.; Weinhold, Nils; Chan, Timothy A.

doi:10.1016/j.cell.2017.09.028

Cited by 1,557 publications

(1,948 citation statements)

References 76 publications

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“…A high frequency of patients switching from chemotherapy to nivolumab in Editorial Nivolumab as first-line treatment in non-small cell lung cancer patients-key factors: tumor mutation burden and PD-L1 ≥50% Patients characteristics were in favor of the chemotherapy group (e.g., fewer liver metastasis, smaller tumor burden and higher proportion of women). It has been previously observed that patients with PD-L1 >50% and high tumor burden benefit from nivolumab administration, however; the number of patients with these characteristics were fewer in the nivolumab group (14). In this study, it was observed that tumor mutation burden on its own is a key factor for nivolumab efficacy and longer median progression free survival.…”

mentioning

confidence: 53%

Nivolumab as first-line treatment in non-small cell lung cancer patients—key factors: tumor mutation burden and PD-L1 ≥50%

Papadopoulos¹,

Maragouli²,

Papatsibas³

et al. 2018

Transl. Lung Cancer Res.

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mentioning

confidence: 53%

Nivolumab as first-line treatment in non-small cell lung cancer patients—key factors: tumor mutation burden and PD-L1 ≥50%

Papadopoulos¹,

Maragouli²,

Papatsibas³

et al. 2018

Transl. Lung Cancer Res.

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“…clones in the TME in the setting of neoantigen loss [129]. The study demonstrates a dramatic remodeling upon anti-PD-1 therapy and provides insight into the mechanism of action.…”

Section: Immune-related Strategiesmentioning

confidence: 99%

“…In one of the recent studies, the authors performed extensive immunogenomic analyses on melanoma samples treated with anti-PD-1 therapy. 68 patients with advanced melanoma, whose diseases progressed on anti-CTLA-4 therapy or were anti-CTLA-4 therapy naïve were employed to characterize how tumor genomic and TME features changed over time after anti-PD-1 therapy [129]. The authors found that mutation and neoantigen load were reduced from baseline in TME among patients who were responding to the therapy [129].…”

Section: Immune-related Strategiesmentioning

confidence: 99%

“…68 patients with advanced melanoma, whose diseases progressed on anti-CTLA-4 therapy or were anti-CTLA-4 therapy naïve were employed to characterize how tumor genomic and TME features changed over time after anti-PD-1 therapy [129]. The authors found that mutation and neoantigen load were reduced from baseline in TME among patients who were responding to the therapy [129]. Analysis of TME heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations.…”

Section: Immune-related Strategiesmentioning

confidence: 99%

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Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

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“…1-7 Over the past years, a panoply of different approaches has been developed or repurposed to (re)initiate anticancer immunity, 8-12 including immune checkpoint blockers targeting cytotoxic T lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) and its main ligand CD274 (best known as PD-L1); 13-19 chemotherapy with immunogenic cell death (ICD) inducers, 20-25 recombinant cytokines, 26,27 monoclonal antibodies (mAbs) that activate co-activatory receptors, 28,29 adoptively transferred T cells engineered to express a tumor-specific chimeric antigen receptor (CAR), 30-36 as well as multiple small molecules targeting distinct immunosuppressive pathways operating within the tumor microenvironment. 37-40 Although some of these strategies have demonstrated unprecedented activity in patients with advanced tumors refractory to several lines of conventional treatment, 41 the fraction of individuals responding to single-agent immunotherapy is generally low, 42-45 arguably with the sole exception of CAR-expressing T cells, which have been associated with >70% overall response rate in pediatric patients with B-cell acute lymphocytic leukemia (ALL).…”

Section: Introductionmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab

Cited by 1,557 publications

References 76 publications

Nivolumab as first-line treatment in non-small cell lung cancer patients—key factors: tumor mutation burden and PD-L1 ≥50%

Nivolumab as first-line treatment in non-small cell lung cancer patients—key factors: tumor mutation burden and PD-L1 ≥50%

Complex interplay between tumor microenvironment and cancer therapy

Trial watch: Peptide-based vaccines in anticancer therapy

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