Understanding the tumor microenvironment for effective immunotherapy

Abstract

Advances in immunotherapy have led to durable and long‐term benefits in a subset of patients across a number of solid tumor types. Understanding of the subsets of patients that respond to immune checkpoint inhibitors at the cellular level, and in the context of their tumor microenvironment (TME) is becoming increasingly important. The TME is composed of a heterogeneous milieu of tumor and immune cells. The immune landscape of the TME can inhibit or promote tumor initiation and progression; thus, a deeper understanding of tumor immunity is necessary to develop immunotherapeutic strategies. Recent developments have focused on characterizing the TME immune contexture (type, density, and function) to discover mechanisms and biomarkers that may predict treatment outcomes. This has, in part, been powered by advancements in spatial characterization technologies. In this review article, we address the role of specific immune cells within the TME at various stages of tumor progression and how the immune contexture determinants affecting tumor growth are used therapeutically.

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

“…Clarifying the mechanisms of tumor immune evasion and immune drug resistance are necessary for improving clinical outcomes for patients. Accumulating evidence has confirmed abnormalities in the tumor microenvironment (TME) were correlated with the efficacy of PD-1/PD-L1 blockade and the angiogenic factors could contribute to the immunosuppression in the TME by inducing vascular abnormalities, suppressing antigen presentation and immune effector cells (28)(29)(30)(31).…”

“…Generally, high MSI is correlated with a stronger immune response ( 57 ) and patients with high-TMB are more likely to benefit from ICIs ( 58 , 59 ). Infiltration of immune cells and the function of immune cells in the tumor microenvironment serve as prognostic factors in predicting the response ( 29 , 60 ). Recent studies also indicated that the gut microbiome was associated with the efficacy of ICIs ( 61 , 62 ).…”

The Pandora’s box of novel technologies that may revolutionize lung cancer

“…Understanding the complex cell types that make up the TME and how they interact sheds light on malignant primary and secondary lung cancers [45,46]. Treatment failure and resistance in primary and secondary lung tumours have revealed that these cells exhibit extensive inter-and intra-tumoural heterogeneity [42,45].…”

“…Treatment failure and resistance in primary and secondary lung tumours have revealed that these cells exhibit extensive inter-and intra-tumoural heterogeneity [42,45]. As a result, understanding the molecular relationship between cell types and their morphological and pathological characteristics is critical [45,46]. Since the late 1990 s, when in-situ sequencing methods to genomic hybridization were developed, the field of spatial biology has grown rapidly, particularly in the last five years [47,48].…”

IL-2 stromal signatures dissect immunotherapy response groups in non-small cell lung cancer (NSCLC)

“…Of these cases, long-term benefit to PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are observed in only 20-30%. There is currently an unmet clinical need for predictive biomarkers for ICI therapy 2–4 . Both membranous tumour cell expression of PD-L1 5 and tumour mutation burden (TMB) 6, 7 are FDA approved companion diagnostic biomarker tests used to stratify patients for immunotherapy, however these appear to be independent variables in their predictive capacity 6, 8, 9 .…”