Cancer immune escape: the role of antigen presentation machinery

In the last decade, a plethora of immunotherapeutic strategies have been designed to modulate the tumor immune microenvironment. In particular, immune checkpoint (IC) blockade therapies present the most promising advances made in cancer treatment in recent years. In non-small cell lung cancer (NSCLC), biomarkers predicting response to IC treatments are currently lacking. We have recently identified Immunoscore-IC, a powerful biomarker that predicts the efficiency of immune-checkpoint inhibitors (ICIs) in NSCLC patients. Immunoscore-IC is an in vitro diagnostic assay that quantifies densities of PD-L1+, CD8+ cells, and distances between CD8+ and PD-L1+ cells in the tumor microenvironment. Immunoscore-IC can classify responder vs non-responder NSCLC patients for ICIs therapy and is revealed as a promising predictive marker of response to anti-PD-1/PD-L1 immunotherapy in these patients. Immunoscore-IC has also shown a significant predictive value, superior to the currently used PD-L1 marker. In colorectal cancer (CRC), the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab improved progression-free survival (PFS) in patients with previously untreated metastatic CRC. In the AtezoTRIBE trial, Immunoscore-IC emerged as the first biomarker with robust predictive value in stratifying pMMR metastatic CRC patients who critically benefit from checkpoint inhibitors. Thus, Immunoscore-IC could be a universal biomarker to predict response to PD-1/PD-L1 checkpoint inhibitor immunotherapy across multiple cancer indications. Therefore, cancer patient stratification (by Immunoscore-IC), based on the presence of T lymphocytes and PD-L1 potentially provides support for clinicians to guide them through combination cancer treatment decisions.

show abstract

“…In other cases, the immune system fails to react to cancer cells, allowing tumors to escape and thus grow unchecked. 3 …”

Section: Introductionmentioning

confidence: 99%

Light on life: immunoscore immune-checkpoint, a predictor of immunotherapy response

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Consecutively, CD8+ T cells, through their T-cell receptors, recognize specific neoantigen peptide/MHC-I complexes, which trigger a cytotoxic immune response against cancer cells presenting specific neoantigen-derived peptides [ 11 ]. Interestingly, one major mechanism through which many tumours may avoid anti-tumour immunity is the downregulation of MHC-I, which causes reduced recognition by- and cytotoxicity of CD8+ T cells [ 12 , 13 ]. Despite that MHC-I downregulation poses a huge challenge for current T-cell engaging immunotherapies, the understanding of the nature of dysregulation provides an opportunity to restore MHC-I expression in adult tumours.…”

Section: Introductionmentioning

confidence: 99%

Strategies to overcome low MHC-I expression in paediatric and adult tumours

Guillaume,

Perzolli,

Boes

2023

Immunotherapy Advances

View full text Add to dashboard Cite

Summary Immunotherapy has made significant advancements in cancer treatments, improving patients’ survival rates and quality of life. Several challenges still need to be addressed, which include the considerable fraction of incomplete curative responses in cancer patients, the development of therapy resistance by tumours, and the occurrence of adverse effects, such as inflammatory and autoimmune complications. Paediatric tumours usually exhibit lower responsiveness to immunotherapies compared to adult tumours. Although the underlying reasons are not yet fully understood, one known mechanism by which tumours avoid immune recognition is through reduced cell surface expression of major histocompatibility complex class I (MHC-I) complexes. Accordingly, the reduced presentation of neoantigens by MHC-I hinders the recognition and targeting of tumour cells by CD8+ T cells, impeding T-cell-mediated cytotoxic anti-tumour responses. MHC-I downregulation indeed often correlates with a poorer prognosis and diminished response to immunotherapy. Understanding the mechanisms underlying MHC-I downregulation in different types of paediatric and adult tumours is crucial for developing strategies to restore MHC-I expression and enhance anti-tumour immune responses. We here discuss progress in MHC-I-based immunotherapies against cancers.

show abstract

“…However, immune responses can be diminished by escape mechanisms employed by ever-evolving tumor cells and pathogens. Escape mechanisms often lead to acquired resistance to therapies ( 3 – 6 ). Crosstalk among a heterogeneous group of immune cells determines the therapeutic outcomes of immunotherapies.…”

mentioning

confidence: 99%

“…An unproductive cancer antigen processing and presentation remains a dominant mechanism of immune escape ( 3 , 21 – 23 ). Seliger and Massa highlighted how activation of oncogenic pathways and inactivation of tumor suppressor genes produces hypoxic tumor-promoting TME.…”

mentioning

confidence: 99%

“…The findings suggest that Rituximab eliminates residual malignant cells by potentiating viral antigen cross-presentation to promote EBV-specific memory T-cell with high cytotoxic capacity. An unproductive cancer antigen processing and presentation remains a dominant mechanism of immune escape (3,(21)(22)(23). Seliger and Massa highlighted how activation of oncogenic pathways and inactivation of tumor suppressor genes produces hypoxic tumorpromoting TME.…”

mentioning

confidence: 99%

See 1 more Smart Citation