Tumor Microenvironment

doi:10.1007/978-3-030-38862-1

Cited by 13 publications

(2 citation statements)

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“…Tumor antigen depletion is a concerning consequence of immunotherapy since increased recognition is desirable and required for tumor elimination. In solid tumors, one contributor to this problem is T cell exclusion ( Pai et al, 2020 ). However, should effective treatment and robust tumor recognition lead to relapse, the resulting tumor has a greater chance of being TAA-depleted ( Rosenthal et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Optimal cancer evasion in a dynamic immune microenvironment generates diverse post-escape tumor antigenicity profiles

George

Levine

2023

eLife

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The failure of cancer treatments, including immunotherapy, continues to be a major obstacle in preventing durable remission. This failure often results from tumor evolution, both genotypic and phenotypic, away from sensitive cell states. Here, we propose a mathematical framework for studying the dynamics of adaptive immune evasion that tracks the number of tumor-associated antigens available for immune targeting. We solve for the unique optimal cancer evasion strategy using stochastic dynamic programming and demonstrate that this policy results in increased cancer evasion rates compared to a passive, fixed strategy. Our foundational model relates the likelihood and temporal dynamics of cancer evasion to features of the immune microenvironment, where tumor immunogenicity reflects a balance between cancer adaptation and host recognition. In contrast with a passive strategy, optimally adaptive evaders navigating varying selective environments result in substantially heterogeneous post-escape tumor antigenicity, giving rise to immunogenically hot and cold tumors.

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Section: Discussionmentioning

confidence: 99%

Optimal cancer evasion in a dynamic immune microenvironment generates diverse post-escape tumor antigenicity profiles

George

Levine

2023

eLife

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“…The host immune response in the tumor microenvironment has recently caught growing interest for its prognostic impact in several solid tumors. 1 With the introduction of new immunotherapeutic agents in the therapeutic armamentarium, immune tumor microenvironment has been extensively investigated, with the aim of identifying features of tumor immunogenicity able to predict benefit from immune-checkpoint inhibitors (ICIs) in different clinical scenarios. 2 …”

Section: Introductionmentioning

confidence: 99%

Dissecting tumor lymphocyte infiltration to predict benefit from immune-checkpoint inhibitors in metastatic colorectal cancer: lessons from the AtezoT RIBE study

Moretto

Rossini

Catteau³

et al. 2023

J Immunother Cancer

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BackgroundTumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC).MethodsWe characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features.ResultsOut of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen <0.20). In the pMMR population, longer progression-free survival (PFS) was reported for Immunoscore-high and Immunoscore-IC-high groups compared with Immunoscore-low (16.4 vs 12.2 months; HR: 0.55, 95% CI: 0.30 to 0.99; p=0.049) and Immunoscore-IC-low (14.8 vs 11.5 months; HR: 0.55, 95% CI: 0.35 to 0.85; p=0.007), respectively, with a significant interaction effect between treatment arms and Immunoscore-IC (p for interaction: 0.006) and a trend for Immunoscore (p for interaction: 0.13). No PFS difference was shown according to TILs and PD-L1 expression. Consistent results were reported in the overall population.ConclusionsThe digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.

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