The odds of immunotherapy success

@article{Gubin2015TheOO,
  title={The odds of immunotherapy success},
  author={Matthew M Gubin and Robert D. Schreiber},
  journal={Science},
  year={2015},
  volume={350},
  pages={158 - 159}
}
Mutation load correlates with the response of melanomas to immunotherapy [Also see Report by Van Allen et al.] Cancer immunotherapy has advanced to the forefront of molecular medicine as a consequence of the success of monoclonal antibodies (mAbs) that block immune checkpoints. Such antibodies, like ipilimumab, reverse cancer-induced immunosuppression and induce durable therapeutic responses in certain cancer patients (1). However, because only some patients respond to checkpoint blockade… 
View on Science
ncbi.nlm.nih.gov
72 Citations
Background Citations
2

72 Citations

Citation Type

Citation Type

The dawn of “immune-revolution” in children: early experiences with checkpoint inhibitors in childhood malignancies
TLDR
The significant proportion of pediatric cancers with high number of mutations and subsequent high expression of neoantigens, together with the potential prognostic role of the immunosuppressive checkpoint molecules can represent a promising rationale that support the use of checkpoint inhibitors.
Genomics- and Transcriptomics-Based Patient Selection for Cancer Treatment With Immune Checkpoint Inhibitors: A Review.
TLDR
Genomics provides powerful tools for the identification of biomarkers for response to immune checkpoint blockade, given their potential to analyze multiple parameters simultaneously in an unbiased manner.
Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors
TLDR
This review critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety.
Immunogenomics of Colorectal Tumors: Facts and Hypotheses on an Evolving Saga.
Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations
TLDR
Clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
The Cancer Immunotherapy Biomarker Testing Landscape.
TLDR
The cancer immunotherapy field, including the use of biomarker testing to predict patient response, is still in evolution, and several categories of tumor and patient characteristics underlying immune responsiveness are emerging and may represent the next generation of cancer Immunotherapy predictive biomarkers.
Controversies on the possible role of immune checkpoint inhibitors in pediatric cancers: balancing irAEs and efficacy
TLDR
It was concluded that no benefit could be expected from further monotherapy trials employing other ICIs with the same mechanism of action until more scientific knowledge becomes available and ICIs could be useful in combination with other therapies to prevent the functional inactivation of several pathways in the hostile microenvironment.
Resistance to Immune Checkpoint Blockade: Mechanisms, Overcoming Resistance, and Future Directions
Prospects for combining targeted and conventional cancer therapy with immunotherapy
TLDR
New insights into the effects of targeted therapies, along with conventional chemotherapy and radiation therapy, on the induction of antitumour immunity will help to advance the design of combination strategies that increase the rate of complete and durable clinical response in patients.
Recent advances in immuno‐oncology and its application to urological cancers
TLDR
Critical areas of future immuno‐oncology research include the prospective identification of patients who will respond to current immune‐based cancer therapies and the identification of new therapeutic agents that promote immune priming in tumours, and increase the rate of durable clinical responses.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 15 REFERENCES
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma
TLDR
Investigating the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab found no recurrent neoantigen peptide sequences predicted responder patient populations, suggesting detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.
Genetic basis for clinical response to CTLA-4 blockade in melanoma.
TLDR
These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti-CTLA- 4 agents are being considered.
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
TLDR
Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment.
TLDR
A growing body of evidence suggests that a major subset of patients with advanced solid tumors shows evidence for a T-cell-inflamed tumor microenvironment, suggesting that the attempt by the host to generate an anti-tumor immune response reflects a biologic process associated with improved patient outcomes.
PD-1 blockade induces responses by inhibiting adaptive immune resistance
TLDR
It is shown that pre-existing CD8+ T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy.
Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens
TLDR
Tumour-specific mutant proteins are identified as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and it is shown that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy.
Tumor neoantigens: building a framework for personalized cancer immunotherapy.
It is now well established that the immune system can recognize developing cancers and that therapeutic manipulation of immunity can induce tumor regression. The capacity to manifest remarkably…
The future of immune checkpoint therapy
TLDR
The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
TLDR
Evaluated data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is re-invigorated on antibody treatment, as well as across multiple cancer types.
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
TLDR
This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab, and high somatic mutation loads were associated with prolonged progression-free survival.
...
1
2
...