Intratumoral heterogeneity in cancer progression and response to immunotherapy

Vitale, Ilio; Shema, Efrat; Loi, Sherene; Galluzzi, Lorenzo

doi:10.1038/s41591-021-01233-9

Cited by 416 publications

(255 citation statements)

References 170 publications

Supporting

Mentioning

254

Contrasting

Order By: Relevance

“…This variability in response to the intensity for each MM cell line did not affect the significance of our results on the melanoma cells when compared to those observed on normal fibroblasts or those obtained with D6 or curcumin itself. Oppositely, this may highlight the necessity of “targeted treatments” accordingly in the different molecular features among the same tumor (tumor heterogeneity), reflecting the propensity for precision medicine for treating cancer, which is recently gaining ground [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells

Pisano

Dettori

Fabbri

et al. 2021

IJMS

View full text Add to dashboard Cite

Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 ± 0.5 μM for 11 and 2.0 ± 0.7 μM for 12) and no toxicity of normal fibroblasts up to 32 µM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed long-lasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells

Pisano

Dettori

Fabbri

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Likewise, the makeup of antigen presenting cells as a crucial factor for efficient immune activation has been insufficiently described. Ideally, all the information should be decoded in a spatiotemporal context (19). As a relevant example, tertiary lymphoid structures (TLS) in human cancer, which are highly organized cellular aggregates resembling lymph nodes, have recently emerged as key sites for the generation of antitumor immunity with a prominent impact on disease outcome and immunotherapeutic response (118)(119)(120)(121).…”

Section: Outstanding Questions and Future Prospectsmentioning

confidence: 99%

“…Extensive studies have been focused on dissecting the cellular and molecular mechanisms underlying the immune response of UBC, in order to identify clinical biomarkers to predict ICI treatment efficacy, and to design novel single or combination trials of more effective regimens (15)(16)(17). Accumulative evidence suggests that tumor cells and the associated nontumor constituents in UBC microenvironment interact to modulate cancer immunogenicity and immunotherapeutic outcomes (18)(19)(20). Therefore, a comprehensive characterization of diverse cell types and states in the context of UBC oncogenesis and treatment is of paramount importance.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis

Zang

Yang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. With technological developments and protocol refinements, single-cell approaches have become powerful tools that provide unprecedented insights into the kaleidoscopic tumor microenvironment and intricate cell-cell communications. In this review, we summarize recent applications of single-cell analysis in characterizing the UBC multicellular ecosystem, and discuss how to leverage the high-resolution information for more effective immune-based therapies.

show abstract

“…It is now clear that most tumors are complex ecosystems that emerge and evolve under robust selective pressure from their microenvironment (TME), which involves immunological, trophic, metabolic, and therapeutic factors. Such pressure promotes the differentiation of both malignant and nonmalignant (i.e., endothelial, stromal, and immune) cells of the TME, culminating in disparate degrees of intratumoral heterogeneity, and resulting in disease progression and resistance to specific treatment [ 43 , 44 ]. Progressing tumors tend to acquire driver mutations that favor some degree of genetic instability, and immunoescape (for example, loss of major histocompatibility complex (MHC) class I-coding genes or capacity to release suppressive cytokines) [ 45 ].…”

Section: The Various Trp Metabolic Pathways and Metabolites In The Rementioning

confidence: 99%

Tryptophan Metabolites at the Crossroad of Immune-Cell Interaction via the Aryl Hydrocarbon Receptor: Implications for Tumor Immunotherapy

Gargaro

Manni

Scalisi

et al. 2021

IJMS

View full text Add to dashboard Cite

The Aryl hydrocarbon receptor (AhR) is a critical regulator of both innate and adaptive immune responses, with potent immunomodulatory effects that makes this receptor an attractive molecular target for novel therapeutics. Accumulating evidence indicates that diverse—both host’s and microbial—tryptophan metabolites profoundly regulate the immune system in the host via AhR, promoting either tolerance or immunity, largely as a function of the qualitative and quantitative nature of the metabolites being contributed by either source. Additional findings indicate that host and microbiota-derived tryptophan metabolic pathways can influence the outcome of immune responses to tumors. Here, we review recent studies on the role and modalities of AhR activation by various ligands, derived from either host-cell or microbial-cell tryptophan metabolic pathways, in the regulation of immune responses. Moreover, we highlight potential implications of those ligands and pathways in tumor immunotherapy, with particular relevance to checkpoint-blockade immune intervention strategies.

show abstract

Intratumoral heterogeneity in cancer progression and response to immunotherapy

Cited by 416 publications

References 170 publications

Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells

Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells

Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis

Tryptophan Metabolites at the Crossroad of Immune-Cell Interaction via the Aryl Hydrocarbon Receptor: Implications for Tumor Immunotherapy

Contact Info

Product

Resources

About