Care of the immunocompromised cancer patient in the perioperative period: Narrative review

Abstract

Cancer is emerging as a significant global public health concern. Worldwide, the incidence of cancer is predicted to increase by 50% by the year 2030. Over 80% of patients will need anaesthetic care and services for perioperative and periprocedural care, as well as for other non-cancer-related procedures. It is estimated that by 2030, over 45 million surgical procedures will be needed globally for cancer control alone. Immunosuppressed patients with cancer represent a unique subset of the population who are at a heightened risk of developing severe infections due to neutropenia, lymphopenia, and immune impairment. The complex nature of the deranged immunologic profiles, compounded by using immune-altering therapies (e.g. corticosteroids, cytotoxic drugs, and immunotherapy) during the perioperative period and after the index surgical procedure, increases the risk of various complications and unfavourable cancer-related outcomes. Therefore, understanding and addressing the unique needs of cancer patients with immune compromise is crucial for improving their prognosis and overall survival rates.

INTRODUCTION

The perioperative period poses unique challenges for the management of immunocompromised cancer patients. The immunosuppressive state is a crucial factor in cancer that significantly affects patient outcomes. It can result from both the tumour’s properties and the treatments used to manage it. Recognising the effects of immunosuppression is vital for developing effective therapies and improving survival rates. Immunosuppression reduces the immune system’s ability to detect and destroy cancer cells. Tumours may evade immune responses by downregulating major histocompatibility complex (MHC) molecules or releasing immunosuppressive cytokines, allowing unchecked tumour growth and increased metastasis. Additionally, immunosuppression can weaken the response to conventional treatments, such as chemotherapy and radiation, leading to reduced tumour regression and higher recurrence rates. These individuals are particularly vulnerable due to the combined effects of cancer and its therapies, leading to an increased risk of infections, complications, and adverse outcomes. The general concern for perioperative physicians is to avoid extrinsic factors affecting the immune system and minimise the risk of complications.[1] This article discusses the causes of immunocompromise in cancer patients, the implications of anaesthetic agents, and strategies for optimising care during the perioperative period.

METHODS

Search strategy and source selection

This narrative review addresses the concerns of immunocompromised patients during the perioperative period.

Relevant Databases: PubMed, Embase, Medline, Scopus, and Web of Science.

Search Terms: Cancer and immunosuppression, immunosurveillance, perioperative stress response, anaesthesia and the inflammatory-immune response, cancer and glucose management, temperature management, immunosuppression and blood transfusions, nutrition, and perioperative immune-boosting therapies.

Inclusion/Exclusion Criteria: Included studies published in English between January 2002 and March 2025, focusing on immunocompromised cancer patients in the perioperative period. Excluded studies include those unrelated to perioperative care and those published in languages other than English.

PATHOPHYSIOLOGY OF IMMUNOSUPPRESSION AND CANCER

Immunosuppression is a hallmark of cancer that significantly contributes to tumour growth and metastasis. The relationship between the immune system and cancer is complex, characterised by an interplay of various cellular and molecular mechanisms. Understanding the aetiology of immunosuppression in cancer is critical for the development of effective therapeutic strategies aimed at enhancing anti-tumour immunity. Under normal circumstances, the immune system plays a crucial role in surveilling and eliminating malignant cells through mechanisms such as recognising tumour antigens, activating cytotoxic T-cells, and producing cytokines. However, when immunosuppression occurs, the body’s ability to mount an effective immune response against neoplastic cells is severely impaired, allowing these cells to proliferate and evade detection.

MECHANISMS OF IMMUNOSUPPRESSION IN CANCER

The immunocompromised state in cancer patients is multifactorial, involving a complex interaction between tumour cells, the immune system, and the surrounding microenvironment. Immunosuppression in cancer is associated with both the malignancy and its treatment. Figure 1 illustrates the primary causes of immunosuppression in cancer patients.

Figure 1.

Causes of immunosuppression in cancer

Tumour microenvironment: The tumour microenvironment (TME) is a complex, immunosuppressive environment that supports tumour progression and metastasis. It includes various immune cells such as tumour-associated macrophages (TAM), tumour-associated neutrophils (TAN), myeloid-derived suppressor cells (MDSC), immature dendritic cells (iDCs), B-cells, natural killer (NK) cells, and regulatory T-cells (Tregs). Tumour-derived soluble factors (TDSFs), such as vascular endothelial growth factor (VEGF), transforming growth factor β (TGF β) interlukin-10 (IL 10), secreted by cancer and immunosuppressive cells, enhance this process. VEGF promotes the differentiation of bone marrow cells into tumour-infiltrating dentritic cells (TiDCs) and TAMs, which contribute to immune evasion by increasing reactive oxygen species (ROS) concentrations that inhibit T-cell activation. Additionally, cancer cells can decrease antigen presentation and upregulate immune checkpoints on immunosuppressive cells to escape immune recognition.[2]

Tumour-Induced Modulation of Immune Cells: At the cellular level, the immune system plays a critical role in recognising and eliminating transformed cells. T lymphocytes, particularly CD8+ cytotoxic T-cells, play a pivotal role in identifying and destroying tumour cells. Additionally, natural killer (NK) cells contribute to the immune surveillance of tumours. When immunosuppression occurs, either through intrinsic host factors or extrinsic exposures, the effectiveness of these immune mechanisms diminishes.

Cytokine Environment: The tumour microenvironment is characterised by an abundance of immunosuppressive cytokines, including IL-10, TGF-β, and IL-6. These cytokines can change the differentiation and function of immune cells, contributing to a state of immunosuppression. For example, TGF-β promotes the differentiation of naive T-cells into regulatory T-cells (Tregs) while simultaneously inhibiting Th1 and Th2 responses. Often elevated during inflammatory states, these cytokines can encourage tumour growth and survival. The interaction between inflammation and immune evasion creates a complex environment that allows tumours to thrive.[3]

Systemic Factors: Apart from local tumour-induced mechanisms, systemic factors also play a crucial role in the immunosuppressive landscape in cancer patients. Chronic inflammation, a common state in cancer, can lead to systemic immune dysregulation and contribute to the tumourigenic process.[4]

Nutritional Status: Cancer and its treatments often result in alterations in nutrition, either due to malabsorption, increased metabolic demand, or side effects such as nausea and vomiting. These factors can further impair immune function. Deficiencies in essential nutrients, such as vitamins A, C, and D, as well as key minerals, can impair the proliferation and differentiation of immune cells. Furthermore, cachexia, a syndrome characterised by weight loss, muscle wasting, and systemic inflammation, also contributes to a compromised immune system, leaving patients more vulnerable to infections and reducing their ability to tolerate treatment.[5]

Comorbid Conditions: The presence of comorbidities, such as diabetes, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases, can worsen immunosuppression in cancer patients. These conditions often lead to chronic systemic inflammation and metabolic dysregulation, which further impair the immune response. Management of comorbid conditions is vital in creating a comprehensive care plan that improves immune function during cancer treatment.[6]

Psychological Factors: Psychological stress is another key contributor to immunosuppression in cancer patients. Elevated levels of stress can lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased cortisol levels, which are known to have immunosuppressive effects. Enhancing psychological well-being through supportive care, counselling, and stress management techniques can potentially enhance immune responses and improve overall treatment outcomes.[7]

Therapeutic Interventions: Cancer treatments can significantly alter immune profiles. These medications can inhibit lymphocyte activation and proliferation, thereby diminishing the immune system’s ability to recognise and eliminate cancerous cells.

Chemotherapy: Chemotherapy interferes with DNA synthesis and repair, acts on immune cells, causing alterations in cell function, cell communication, and signalling pathways, leading to cytotoxic effects on the body. Such immune suppression can weaken the anti-tumour immune response and increase the risk of immune-related toxicities.[8]

Radiation Therapy: Radiation therapy damages DNA and hampers cell division, leading to cell death. The resulting cell death releases various components that can either suppress or stimulate the immune response. Within the tumour microenvironment, a strong inflammatory response is triggered, releasing mediators such as damage-associated molecular patterns (DAMPs), reactive oxygen and nitrogen species, cytotoxic cytokines, TGF-β1, tumour necrosis factor-alpha (TNF-α), interleukins, and heat shock proteins (HSP). These can activate both the innate and adaptive immune systems.[9]

Immunotherapies: Immunotherapy is used to treat various cancers at both early and late stages of the disease. The drugs involved in immunotherapy include targeted antibodies, immune checkpoint inhibitors, cell-based immunomodulators, vaccines, and oncolytic viruses. These treatments help the immune system recognise and destroy cancer cells by targeting proteins, such as programmed cell death protein-1 (PD-1) and its ligand, PD-L1. Generally, immunotherapies are effective and tend to have fewer systemic toxicities compared to chemotherapy; however, their long-term effects are still being studied. Additionally, they are often used in combination with other treatment modalities.[10]

The mechanism of action for immunotherapy involves relieving the inhibition of activated T-cells, which leads to increased T-cell activation and, potentially, the destruction of normal cells. The adverse events associated with immunotherapy are well-documented. These can include inflammatory and autoimmune responses, as well as the activation of underlying latent chronic diseases. Such effects may decrease the host’s defences and increase the risk of opportunistic infections, ultimately compromising treatment effectiveness and overall patient survival.[11]

As research continues to unfold in this burgeoning field, it becomes increasingly clear that understanding the intricate pathophysiology of immunosuppression-related cancer is crucial for developing effective prevention and therapeutic strategies. It emphasises the importance of tailored immunotherapies that can reinvigorate immune responses against tumours in patients who are at an increased risk due to immunocompromised states.

CONSEQUENCES OF AN IMMUNOSUPPRESSIVE STATE IN CANCER PATIENTS

Immediate Effects of Immunosuppression in the Perioperative Period: There is an alteration in the inflammatory-immune state and response to surgery.

Surgery: Surgical resection is a key treatment for solid tumours. The stress from surgery activates the HPA axis and the sympathetic nervous system (SNS), which together suppress cell-mediated immunity (CMI) by affecting natural killer (NK) cells and T-cells through the programmed cell death pathway (PD-1 and PD-L1). This process reduces immune-stimulating cytokines, such as IL-1, IL-2, and interferon (IFN)-γ, while increasing immunosuppressive cytokines, including IL-10. This immunosuppressive state can develop within hours and may persist for several days to 6 months, depending on the extent of tissue damage. Adjuvant therapies are often needed after surgery to combat the minimal residual disease, as well as the immunosuppressive window after surgery.[12]

Wound Healing: Signalling molecules such as transforming growth factor-α (TGF-α) and TGF-β, insulin-like growth factor I and II (IGF I and II), vascular endothelial growth factor (VEGF), platelet-derived growth factor, and T-lymphocytes play an essential role in different stages of wound healing. The immunocompromised patient has an altered immune response, negatively affecting wound healing. Bevacizumab, a VEGF inhibitor, when initiated within 28 days of surgical intervention, delays wound healing and is associated with a 3.4% increase in wound infection rate and a 13% complication rate if surgery is performed during treatment.[13,14]

Infection: Improved cancer care and ongoing therapies during survivorship have led to longer life expectancies. However, this extended survivorship may result in a prolonged immunosuppressed state. Consequently, patients may face new treatment-related complications and increased vulnerability to opportunistic and severe infections. Sepsis, a severe infection that can lead to death, is a common outcome for these patients. The overall mortality rate for individuals with sepsis is 50% higher than that of the general population. Mortality rises to approximately 40% for those under the age of 45, but beyond that age, it becomes less dependent on age and more related to the number of organ systems affected.[15]

Symptom Burden-Fatigue: More than 90% of cancer patients experience one or more symptoms directly caused by the disease or its treatment. These symptoms negatively affect the completion of planned treatments and the patients’ health-related quality of life (HRQoL).[16,17] For immunocompromised patients, the ‘burden of disease’ indicates a significantly higher risk of developing severe complications from infections, even those caused by common illnesses.[18]

Prolonged Hospital Stay: The immunocompromised patient is at considerable risk for surgical site infection (SSI) in the perioperative period and increased hospital length of stay. Wound management, surgical dressing techniques, perioperative steroids, immunomodulatory drugs, and various wound healing medications have been studied, but no conclusive results have been found. Precise methods to reduce SSI and thus reduce hospital length of stay have not been found. The general method defined by the WHO is adherence to SSI care bundles and guidelines for managing patients at all stages of the perioperative period.[19]

REMOTE EFFECTS OF IMMUNE SUPPRESSION IN SURGICAL AND CANCER OUTCOMES

Understanding the remote effects of immunosuppression on surgical and cancer outcomes is imperative for enhancing patient care and refining therapeutic strategies.

Inflammatory Markers: Surgery triggers a stress response that activates the hypothalamic-pituitary-adrenal axis, leading to the release of cortisol and catecholamines. These substances elevate pro-inflammatory cytokines, such as IL-6 and IL-8, as well as immunosuppressive cytokines, including IL-4, IL-10, TGF-β, and VEGF. An imbalance between pro- and anti-inflammatory responses can disrupt cellular immunity and foster tumour recurrence.[20,21] Recent guidelines for enhanced recovery after surgery (ERAS) programs include components designed to reduce surgical stress and the inflammatory response during the perioperative period, while maintaining immune competence.[22]

Surveillance: The concept of immunosurveillance dates back to Paul Ehrlich’s study of foetal development in 1909, where he stated, ‘In the enormously complicated course of foetal and post-foetal development, aberrant cells become unusually uncommon’.[23] At the time, experimental tools were not available to prove his theory. The immune system identifies tumour cells through tumour-specific antigens, activating memory and effector cells that target and destroy these cells. Higher counts of lymphocytes and NK cells are associated with improved survival in patients with colon, prostate, and ovarian cancer. Regulatory T-cells activate CD4+ and CD8+ cells to target tumours, facilitating immunosurveillance. Immunocompromised patients show deficiencies in adaptive immune responses, particularly affecting T-cell function, which hinders the detection and elimination of tumours.[24]

Recurrence: Several perioperative factors, including the inflammatory response to surgery, hypothermia, and blood transfusion, contribute to relative immunosuppression, leading to poorer outcomes in immunocompromised patients. The activation of the sympathetic nervous system and the HPA axis releases stress hormones, such as catecholamines and prostagalndin E2, which can increase tumour invasiveness and recurrence while downregulating immune cell activity.[25] Strategies to reduce cancer recurrence during the perioperative period, such as combining beta-blockers with cyclo-oxygenase 2 (COX-2) inhibitors, show promise; however, COX-2 inhibitors such as celecoxib can further suppress the immune system, making immunocompromised patients more susceptible to infections. If necessary, close monitoring for illness is essential in these patients. Additionally, alternative treatments should be considered whenever possible.[26,27,28]

Risk for Other Cancers: A specific population is the post-transplant immunocompromised patient. Patients with severe immune dysregulation post-transplant have a doubled risk of developing various cancers, particularly those linked to oncogenic viruses, such as hepatocellular carcinoma and cervical cancer. While cancer immunotherapy has been developed due to this increased risk, focus has been primarily on melanoma, treated with IL-2 and checkpoint inhibitors. These monoclonal antibodies block tumour checkpoint proteins to enhance anti-tumour T-cell responses and show effectiveness against melanoma, non-small cell lung carcinoma, renal cell carcinoma, and cutaneous squamous cell carcinoma. Response rates vary, but treatments can lead to complete responses, especially in cancers with high tumour mutational burden (TMB) outcomes.[29]

ANAESTHETIC AGENTS AND MODIFIABLE PERIOPERATIVE FACTORS ON IMMUNITY

Table 1 illustrates anaesthetic agents and the perioperative factors reported to affect the perioperative immunity of patients undergoing cancer surgeries.

Table 1.

Anaesthetic agents and the perioperative factors reported to affect the perioperative immunity of patients undergoing cancer surgeries

Factors	Impact
Anaesthetic Agents	• Immunomodulatory properties worsen immunosuppression. •Contribute to the progression of disease. •Immune-boosting properties may enhance immune function. •Anti-inflammatory properties improve outcomes.
Volatile Agents	• Immunosuppressive effects show a range of conflicting outcomes. •Depress natural killer (NK) cell activity, contributing to immunosuppression. •Sevoflurane contributes to disease progression in oestrogen receptor-positive (ER+) breast cancer, but not in non-small cell lung cancer, if lignocaine is added. •Isoflurane’s immunosuppressive effect enhances the upregulation of vascular endothelial growth factor (VEGF), contributing to the progression of disease in prostate and ovarian cancers. •Tailor anaesthetics for optimal patient outcomes.[30]
Intravenous Agents	• Propofol has anti-inflammatory and immune-boosting effects. •Propofol induces apoptosis in cancer cells and enhances the effectiveness of chemotherapy. •No difference in disease recurrence between general anaesthesia with sevoflurane and fentanyl versus regional anaesthesia with propofol.[31] •A meta-analysis illustrates better recurrence-free survival with total intravenous anaesthesia (TIVA) using propofol.[32] •Ketamine inhibits the NMDA receptor, reduces pro-inflammatory markers, and induces apoptosis.[33] •Ketamine attenuates immunosuppression in patients undergoing modified radical mastectomy.[34]
Regional Anaesthesia	• Modulation of neuroimmune interactions at the local level restricts inflammatory pathways. •Decrease in inflammatory biomarkers (IL-6, TNF-a) enhances pain management and facilitates improved recovery.[35]
Opioids	• Immunosuppressive effects. •Morphine worsens cancer progression and increases the risk of postoperative infections. •Buprenorphine does not have these effects. •Combined with immune-therapeutics imatinib or nilotinib, fentanyl can increase sedation due to shared liver metabolism.[36]
Non-steroidal anti-inflammatory Drugs (NSAIDs)	• The cyclooxygenase-2 (COX-2) receptor is present in many cancer cells. •Adjuvant celecoxib improves overall survival in gastric cancer patients with COX-2 expression. •Cost-effective alternatives with anti-tumour effects.[37]
Alpha-2 Agonist	• Reduce inflammation in the perioperative period.[38]
Corticosteroids	•Adaptive and innate immune responses have anti-inflammatory properties.[39] •Effective for brain metastases. •Decrease effectiveness of immune checkpoint inhibitors (ICIs).[40]

CONSIDERATIONS FOR OPTIMISING CARE IN THE PERIOPERATIVE PERIOD

Due to the complex effects of anaesthetic agents and adjustable perioperative factors on the immune system, a thorough approach to patient management during the perioperative period is essential. Figure 2 illustrates strategies that can be employed to protect immunocompromised cancer patients during the perioperative period. Table 2 illustrates perioperative strategies to improve patient outcomes.

Figure 2.

Perioperative modifiable factors

Table 2.

Perioperative strategies to improve patient outcomes

Keypoint	Remarks
Preoperative Optimisation	• Identify specific risk factors. •Identify extent of immunosuppression due to the primary disease and treatments.
Patient Education	• Educate patients about the importance of preoperative preparation, including lifestyle changes to bolster immune function.
Multidisciplinary Approach	• Collaboration among oncologists, anaesthesiologists, surgeons, and nurses. •Implement a tailored perioperative plan. •Encompass psychosocial support to improve the patient’s overall well-being.
Symptom Burden	• Monitor and manage symptom burden in the perioperative period. •Increased risk of prolonged hospital stays, increased healthcare costs, and life-threatening situations.
Prehabilitation	• Implemented after chemotherapy and before abdominal surgery increases physical performance and improves postoperative outcomes.[41]
Glucose Management	• Hyperinsulinemia and chronic inflammation contribute to Diabetes Mellitus (DM) in up to 18% of patients. •Type 2 diabetes mellitus (T2DM) patients are at a higher risk of cancer mortality, 18% higher for all cancers, 9% for breast cancer, and 2.4 times higher for colorectal cancer. •Targeted therapies (tyrosine kinase inhibitors (TKIs)) cause hyperglycaemia in 15% to 50% of patients within the first 3–4 weeks of therapy.[42] •Hyperglycaemia is a risk factor for infection, poor wound healing, sepsis, and ketoacidosis, and requires escalation of care.[43]
Temperature Management	• Mild hypothermia increases the risk of wound infections, postoperative ischemic myocardial events, blood loss, and prolongs recovery. •Maintaining normothermia achieves optimal surgical outcomes, patient safety and satisfaction.[44,45]
Infection Control Practices	• Adherence to strict aseptic techniques and prophylactic antibiotics mitigates the risk of surgical site infections and promotes a healthier immune response. •Early warning systems and rapid response programs are crucial for high-risk cancer patients.[19]
Blood Transfusion	• Blood transfusions alter the immune response. •Negatively impact outcomes across all age groups. •Reduces postoperative survival rates in patients with colorectal cancer. •Activated platelets promote tumour growth.[46]
Anaesthetic agents	• Evidence on the inflammatory and immune responses to anaesthetic agents is inconsistent. •Tailor anaesthetic choices based on the patient’s cancer diagnosis and treatment history. •Customise anaesthetic techniques to the patient’s health status and surgical procedure to mitigate adverse immune effects.
Perioperative immune-boosting therapies	• Perioperative immune-boosting therapies enhance the immune system, leading to better tissue repair.[47] •Immunotherapy Drugs: Enhance T-cell activity to target cancer cells more effectively. •Nutritional Supplements: Vitamin C boosts immune function and reduces tissue damage shortening recovery times. •Immunonutrition: Diets rich in arginine, glutamine, and omega-3 fatty acids improve immune responses. •Cytokines: Regulate inflammation and stimulate immune response. •Potential side effects may include inflammation, cytokine release syndrome, or immune-related adverse events.[48]
Postoperative monitoring	•Close postoperative monitoring identifies complications early. •Prompt intervention for signs of infection.

CONCLUSIONS

While the rate-adjusted incidence of cancer and cancer-related mortality rates have seen a gradual decline in the last three decades in the United States and the developed world, there remains a wide disparity in the delivery of cancer care globally. With changing demographics (increasing life expectancy, survivorship), the advent of new cancer therapies (targeted and immune-therapies), and the need for ongoing cancer therapies to prevent cancer recurrence and treat secondary cancers, there will be an increase in the subset of immunocompromised cancer patients. It is essential to understand the specific perioperative considerations for immunocompromised cancer patients, allowing for optimised perioperative strategies that minimise complications and improve cancer and overall outcomes in this unique patient population. Further research is crucial to elucidate the mechanisms of immunosuppression and to develop novel therapies that can restore immune function and enhance the effectiveness of cancer treatment.

Presentation at conferences/CMEs and abstract publication

None

Study data availability

De-identified data may be requested with reasonable justification from the authors (email to the corresponding author) and shall be shared after approval as per the authors’ institution’s policy.

Disclosure of use of artificial intelligence (AI)-assistive or generative tools

The AI tools or language models (LLM) have not been utilised in the manuscript, except that software has been used for grammar corrections and references.

Declaration of use of permitted tools

All figures and tables are the author’s own work.

Authors contributions

AD was involved in the preparation, literature search, writing, editing, figure and table design creation. VJG was involved in the concept, literature search, preparing, writing and editing of the manuscript.

Conflicts of interest

There are no conflicts of interest.

Supplementary material

NIL.

Funding Statement

This study was supported by a grant from NIH Cancer Grant P30CA008748.