Immunotherapy in Melanoma and Kidney Cancer: Insights from Samra Turajlić at the Francis Crick Institute

In this discussion, Samra Turajlić explains how immunotherapy has reshaped treatment for melanoma and kidney cancer, moving beyond traditional therapies to harness the immune system. The talk covers the concept of cancer as an ecosystem, the role of T cells and natural killer cells, and the impact of immune checkpoints like PD-1 and CTLA-4. Real patient journeys illustrate durable remissions and the potential for adjuvant immunotherapy to reduce recurrence after surgery. The Crick Institute’s lab-based approach to decoding the tumor microenvironment, developing biomarkers, and pursuing novel strategies such as cancer vaccines and engineered immune cells is highlighted, along with the challenges of side effects and the push toward earlier, personalized interventions.

Overview and Personal Journey

Samra Turajlić, a Francis Crick Institute research group leader and practicing oncologist, describes her multifaceted role across Crick, the Royal Marsden Hospital, and Manchester Institute. She explains why melanoma and kidney cancer have historically been grouped together as orphan cancers with limited therapies beyond surgery, and how the advent of immunotherapy over the last decade has transformed outcomes for these malignancies. The talk emphasizes keeping patients at the center of research questions while pursuing deeper scientific insights into how immunotherapies work and why they fail in some patients.

Cancer Immunity and the Tumor Ecosystem

The speaker frames cancer as an ecosystem within which tumor cells interact with a diverse cast of immune and stromal cells, blood vessels, and signaling molecules. While mutations are essential for tumor formation, they are not sufficient to drive cancer on their own. The tumor microenvironment can shield cancer cells and impede immune attack. Immune surveillance normally detects abnormal cells, with T cells and natural killer cells recognizing foreign or stressed antigens. Macrophages and other immune components help clear debris and strengthen immune recognition. When immune surveillance falters or is suppressed, cancers can progress and metastasize. This ecosystem-centric view shapes the future of cancer care, aiming to reshape the environment to make cancer cells more vulnerable to immune attack.

Immunotherapy Milestones and Mechanisms

The talk outlines the evolution of cancer immunotherapy from early cytokine therapies to the discovery of immune checkpoints, which act as brakes on T cell activity. Blocking checkpoints such as PD-1 and CTLA-4 has yielded dramatic survival benefits, with combination therapy providing durable remissions in a subset of patients. The trajectory is illustrated with survival curves showing a plateau years after treatment, suggesting long-term disease control and the potential for cures in some cases. The discussion also notes that while many patients benefit, a substantial proportion do not, underscoring the need to understand who will respond and why.

Clinical Evidence in Melanoma and Kidney Cancer

The presentation highlights how melanoma, driven by a high mutational burden due to UV exposure, is particularly susceptible to immune-based therapies. Durable responses and even potential cures have been observed with combinations that inhibit different checkpoints, and the same principle applies to kidney cancer, albeit with distinct biology. In some trials, adjuvant immunotherapy after surgical resection has reduced relapse risk, while in advanced disease, checkpoint inhibitors have extended survival compared with historical therapies. The narrative is complemented by the personal account of a patient with melanoma who experienced multi-site metastasis and subsequently achieved long-term remission after immunotherapy, illustrating the transformative potential of these treatments when effective.

The Crick Translational Approach and Biomarkers

Turajlić describes a clinic-to-lab feedback loop at the Crick Laboratory, where tumor profiling using advanced technologies informs laboratory experiments that, in turn, guide clinical decisions. A diverse, multidisciplinary team collaborates to map the tumor ecosystem and identify why immunotherapies fail in some patients. Biomarker development is a central aim, enabling better patient selection and more personalized strategies. The research integrates genetics, evolutionary biology concepts, and tumor microenvironment analyses to understand the dynamics of antitumor immunity and resistance mechanisms.

Biology of Resistance and Novel Targets

In melanoma, some tumors acquire resistance through mutations that alter antigen presentation or immune signaling, or through spatial tumor heterogeneity that impedes uniform immune recognition. A key insight is that a high mutational load can be paradoxically associated with resistance if tumor mutations are unevenly distributed, escaping immune detection. In kidney cancer, attention is drawn to endogenous retroviruses as potential novel antigens that become de-repressed in cancer, potentially offering new immunotherapeutic targets. These findings motivate the search for alternative strategies when conventional checkpoint inhibitors fail.

Future Therapies and the Path Forward

The talk surveys emerging therapies that may broaden and deepen responses. Cancer vaccines, including neoantigen-targeted vaccines delivered as peptides or personalized mRNA vaccines, hold promise especially in early disease stages. The field is also exploring living immune cell therapies, such as engineered T cells, though manufacturing complexity and cost pose challenges for wide-scale deployment. In kidney cancer, ongoing work aims to identify T cell receptors that recognize tumor antigens and to pair them with tumor profiling to create personalized cellular therapies. The overarching theme is to move toward memory responses, enabling durable cancer control even after treatment cessation, and to use combinations that create synergistic effects while expanding applicability across cancer types.

Clinical Realities and the Quest for Personalization

Side effects from immunotherapies, including autoimmune manifestations treated with steroids, are acknowledged as a major consideration. The need to predict who will experience adverse events, and to manage them precisely, is highlighted as a critical area for research. The presentation concludes with a call for team science across clinical and basic science disciplines, underpinned by patient involvement, robust funding, and scalable translational pipelines that bring laboratory insights to the clinic and back again.

Closing Reflections

Turajlić emphasizes that immunotherapy has already transformed several solid cancers by enabling durable remissions and reducing relapse risk after surgery. Yet a large proportion of patients still do not benefit, which motivates ongoing efforts to identify biomarkers, develop novel targets, and broaden the therapeutic toolkit. The talk ends with gratitude to the patients, families, collaborators, and funders who support this work and with a reaffirmation that patient-centered research and cross-disciplinary collaboration are essential to realizing the full potential of immunotherapy.