Virtually all successful anticancer treatments either create, restore or enhance the antitumour immune response. Therefore, the specific features of the immune microenvironment, both before and after treatment, are important determinants of patients' outcomes. In a review article published in the Nature Reviews Clinical Oncology, the authors describe the influence of the immunological characteristics of the tumour microenvironment on responses to treatment in patients with a variety of cancers.
Over the past 5 years, the ability to overcome local and systemic immunosurveillance mechanisms has been established as an essential step in tumour evolution, as has the observation that different forms of anticancer treatments owe their therapeutic effectiveness, at least in part, to their capacity to reinstate, or enhance, an anticancer immune response.
The first oncogenic events in the development of a tumour often consist of mutations that allow cells to proliferate independently of the need for growth- promoting signals and/or render the cells insensitive to inhibitory mechanisms. However, such mutations alone generally are not sufficient to drive a non-malignant cell into full malignancy; additional modifications are required to enable uncontrolled proliferation, suppression of cell-death pathways and to evade recognition and destruction by the immune system. During this process, which can often last several years, from the early stages of transformation to the emergence of clinically detectable neoplasia, cancer cells interact with the tumour microenvironment, often taking advantage of local factors that favour the expansion of the tumour, aided by immunosurveillance.
The subsequent step — when cancer cells leave the primary lesion and metastasize through lymphatic and blood vessels to lymph nodes and distant organs — requires a renewed level of escape from immune attack and adaptation to a new microenvironment in the form of the metastatic niche. Successful anticancer immunotherapies are able to modify these tumorigenic interactions between cancer cells and their microenvironment, and enable immune effectors to destroy malignant cells located at both primary and metastatic sites.
Most external agents that initiate tumorigenesis promote chronic inflammation at the tumour sites.
Immunotherapy is currently the most rapidly advancing area in oncology, and provides the opportunity to effectively treat, and even cure, several previously untreatable malignancies. A growing awareness exists of the fact that the success of chemotherapy and radiotherapy also relies on the induction of a durable anticancer immune response.
The local immune infiltrate undergoes dynamic changes that accompany a shift from a pre-existing immune response to a therapy-induced immune response. As a result, the immune contexture, which is determined by the density, composition, functional state and organisation of the leukocyte infiltrate of the tumour, can yield information that is relevant to prognosis, prediction of a treatment response and various other pharmacodynamic parameters.
Several complementary technologies can be used to explore the immune contexture of tumours, and to derive biomarkers that could enable the adaptation of individual treatment approaches for each patient, as well as monitoring a response to anticancer therapies.
The range of methods available to monitor the progression of cancers towards immune escape as well as the positive effects of therapeutic measures on the tumour microenvironment have been continuously expanding over the past years. Perhaps the most important development in the field, however, resides in a switch from a purely cell-autonomous vision of neoplasia to a broader appreciation of the cancer immune microenvironment.
In their article, the authors emphasize on next key points:
- Most cancers have evaded immune control, or immunosurveillance, at the time of presentation; however, residual signs of an active anticancer immune response indicate a positive prognosis.
- Positive immune-related prognostic features include the presence of specific T-lymphocyte subsets, the absence of immunosuppressive elements, the localization of the immune infiltrate and specific features of its organisation.
- Successful anticancer therapies, including cytotoxic chemotherapies and targeted agents, improve the local immune contexture and mediate at least part of their long-term effects by reinstating immunosurveillance.
- The presence of either a pre-existing or induced immune response indicates a more favourable prognosis than that of patients whose tumours lack either of these features.
- Immune-checkpoint inhibitors have a profound effect on the local immune infiltrate, and a variety of biomarkers have the potential to indicate a pre-existing or developing anticancer immune response.
- The discovery of immunological biomarkers in oncology has been facilitated by the advent of ever more sophisticated technologies, posing new challenges to both data integration and bioinformatic analysis.
Fridman WH, Zitvogel L, Sautès–Fridman C, et al. The immune contexture in cancer prognosis and treatment. Nature Reviews Clinical Oncology; Published online 25 July 2017. doi:10.1038/nrclinonc.2017.101