Why the Mouth Matters: Dentists Join the CAR-T Therapy Team

Chimeric antigen receptor T-cell therapy, better known as CAR-T, has transformed the outlook for patients with certain blood cancers, offering durable remissions to people who had exhausted every conventional option. Yet as the technology has matured, clinicians have become increasingly aware that its success depends not only on engineering powerful immune cells but also on managing the cascade of side effects that follows. A new commentary published in Supportive Care in Cancer by Pasquale Niscola and Maria Ilaria Del Principe, two hematologists based in Rome, argues that one corner of supportive care has been persistently neglected: the mouth. The authors call for oral health assessment and preventive dental care to be built formally into the CAR-T treatment pathway, from the first consultation through long-term follow-up.

The biological rationale for this call is straightforward once the mechanics of CAR-T therapy are understood. Before engineered T-cells are infused, patients typically receive lymphodepleting chemotherapy, a regimen designed to suppress their existing immune system so that the infused cells can expand without being rejected. This creates a window of profound immunosuppression, often compounded by severe neutropenia, in which the body’s defenses against bacteria, fungi, and viruses are dramatically weakened. At the same time, many candidates for CAR-T have already been through multiple lines of chemotherapy, which damages the oral mucosa, alters saliva production, and disrupts the delicate microbial ecosystem of the mouth. The result is that even a routine dental infection or an untreated cavity can become a serious systemic threat precisely when the patient is most vulnerable.

The oral cavity is, in fact, one of the most microbiologically dense environments in the human body, harboring hundreds of bacterial species alongside fungi such as Candida albicans. When mucosal barriers break down, as they commonly do during intensive cancer therapy, these microorganisms can translocate into the bloodstream. Recent research on Candida has shown how fungal cells can cross the intestinal epithelial barrier, and the same principle applies to oral tissues. In a patient recovering from lymphodepletion and facing the inflammatory storm of cytokine release syndrome, a dental abscess or fungal overgrowth is not a minor inconvenience; it is a potential source of sepsis, treatment delay, or even failure of the CAR-T product itself. Niscola and Del Principe emphasize that oral infectious complications are among the avoidable hazards that a structured dental evaluation could help prevent.

Evidence supporting this concern is accumulating. A retrospective observational study published in the same journal examined oral manifestations and dental management in patients undergoing CAR-T cell therapy and documented a range of problems, including mucositis, infections, and xerostomia, the distressing dryness of the mouth that follows damage to salivary glands. Related work in patients who have undergone allogeneic hematopoietic stem cell transplantation, a closely related form of cellular therapy, has measured long-term changes in the immunological components of saliva, suggesting that glandular function and mucosal immunity may take months or years to recover, if they recover at all. These findings paint a picture of the mouth as a barometer of systemic vulnerability, one that changes measurably during and after aggressive immunotherapy.

The functional consequences extend beyond infection. New clinical data on swallowing outcomes after CAR-T treatment in patients with non-Hodgkin lymphoma have documented dysphagia, or difficulty swallowing, as a real and underappreciated complication of the therapy pathway. Taste disturbances, or dysgeusia, have also been reported in association with immunotherapy, and recent translational work has explored microbiome-aware nutritional strategies to address them. When eating becomes painful, difficult, or unappetizing, patients lose weight, malnutrition sets in, and recovery slows. Oral health, in other words, is not a cosmetic concern but a determinant of whether a patient can maintain the nutritional and physical resilience needed to weather the acute phase of CAR-T therapy and benefit from it in the long run.

Recognizing these risks, the international supportive care community has begun to respond. In 2025, the Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology issued a joint clinical practice statement recommending dental evaluation and management before treatment for hematologic malignancies and before CAR-T cell therapy. The statement, authored by an expert panel including Zadik, Raber-Durlacher, Epstein, and colleagues, essentially formalizes what dental oncologists have long practiced: that patients scheduled for intensive immunotherapy should undergo a thorough oral examination, radiographic assessment, and stabilization of active disease before their immune system is deliberately dismantled. Niscola and Del Principe’s commentary can be read as both an endorsement of that guidance and a call to close the gap between recommendation and routine practice.

What would such integration look like in practice? The authors sketch a pathway that begins at patient selection, when a candidate for CAR-T is first identified. At that point, ideally weeks before lymphodepletion begins, a dentist or oral medicine specialist would assess caries risk, screen for periodontal disease and non-vital teeth, evaluate the condition of dentures and oral prostheses, and treat any source of potential infection. Preventive measures would include professional cleaning, fluoride application, and patient education on meticulous oral hygiene. During the hospital admission for infusion, the focus shifts to monitoring for mucositis, managing xerostomia with salivary substitutes or stimulants, and watching for early signs of oral candidiasis or herpes simplex reactivation. After discharge, follow-up dental visits would track healing, address persistent dry mouth or taste changes, and restore function as immune reconstitution proceeds.

The commentary also situates oral care within the broader architecture of CAR-T supportive management, which has grown increasingly sophisticated around toxicities such as cytokine release syndrome and immune effector cell-associated neurotoxicity. Guidelines for managing these systemic toxicities are now well established, and the authors suggest that oral supportive care deserves the same systematic attention. They point to their own prior work on mucosal toxicity in hematological malignancies, which reviewed prevention and management strategies across the spectrum of intensive therapies, as part of a growing literature arguing that the mucosal surfaces of the body are a frontline in cancer supportive care. The mouth, being simultaneously a sensory organ, a digestive gateway, and a microbial reservoir, sits at the intersection of several of these concerns.

There are practical challenges to implementing the vision. CAR-T therapy is delivered in a relatively small number of specialized centers, and patients often travel long distances for treatment, which complicates coordination with community dental providers. Many patients arrive with years of neglected dental care, particularly those whose cancer diagnosis interrupted routine checkups, and complete dental rehabilitation can take longer than the clinical window allows. Prioritization therefore becomes essential: treating active infection and removing unstable teeth take precedence over elective work, and the MASCC/ISOO statement offers a framework for triage. The authors argue that embedding a dental assessment checklist into the standard CAR-T workup, much as cardiac and infectious disease evaluations are already routine, would require modest resources but could prevent disproportionate harm.

Ultimately, the message of the commentary is one of integration rather than novelty. CAR-T cell therapy represents one of the most striking achievements of modern medicine, and its expanding applications across hematological malignancies continue to grow, as recent reviews of the field document. But the technology’s promise can only be realized if patients survive and thrive through the treatment window, and that depends on the unglamorous details of supportive care. Oral health, the authors contend, should no longer be an afterthought delegated to chance. By bringing dentists into the multidisciplinary team that plans and delivers CAR-T therapy, centers can reduce infectious complications, preserve nutrition and quality of life, and give patients the best possible chance of enjoying the remissions that this remarkable therapy can deliver.

Subject of Research: Integrating oral health and preventive dental care into CAR-T cell therapy supportive care

Article Title: Integrating oral health and preventive dental care into CAR-T cell therapy

Article References: Niscola, P., & Del Principe, M. I. (2026). Integrating oral health and preventive dental care into CAR-T cell therapy. Supportive Care in Cancer, 34(10), Article 1012. https://doi.org/10.1007/s00520-026-11268-8

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11268-8

Keywords: CAR-T cell therapy, oral health, preventive dental care, supportive care, hematologic malignancies, mucositis, immunosuppression, dysgeusia, dysphagia, oral infections, immunotherapy, MASCC/ISOO guidelines